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1. Supplementary Figure 1 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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2. Supplementary Figure Legend from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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3. Supplementary Table 3 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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4. Supplementary Figure 3 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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5. Supplementary Figure 2 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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6. Supplementary Table 2 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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7. Supplementary Figure 4 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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8. Supplementary Figure 5 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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9. Supplementary Table 1 from Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, primary, Diaconu, Iulia, primary, Koski, Anniina, primary, Cerullo, Vincenzo, primary, Liikanen, Ilkka, primary, Tähtinen, Siri, primary, Oksanen, Minna, primary, Heiskanen, Raita, primary, Pesonen, Saila, primary, Joensuu, Timo, primary, Alanko, Tuomo, primary, Partanen, Kaarina, primary, Laasonen, Leena, primary, Kairemo, Kalevi, primary, Pesonen, Sari, primary, Kangasniemi, Lotta, primary, and Hemminki, Akseli, primary

Published
2023
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10. Data from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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11. Supplementary Table 1 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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12. Supplementary Table 3 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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13. Supplementary Figure 2 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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14. Data from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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15. Supplementary Table 5 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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16. Supplementary Figure 6 from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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17. Supplementary Table 4 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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18. Supplementary Figure 3 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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19. Supplementary Table 2 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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20. Supplementary Figure 5 from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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21. Supplementary Figure 2 from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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22. Supplementary Figure 1 from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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23. Supplementary Figure 3 from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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24. Supplementary Figure 1 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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25. Supplementary Methods from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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26. Supplementary Figure 4 from Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, primary, Kangasniemi, Lotta, primary, Ranki, Tuuli, primary, Kanerva, Anna, primary, Pesonen, Saila K., primary, Gerdemann, Ulrike, primary, Leen, Ann M., primary, Kairemo, Kalevi, primary, Oksanen, Minna, primary, Haavisto, Elina, primary, Holm, Sirkka-Liisa, primary, Karioja-Kallio, Aila, primary, Kauppinen, Satu, primary, Partanen, Kaarina P. L., primary, Laasonen, Leena, primary, Joensuu, Tima, primary, Alanko, Tuomo, primary, Cerullo, Vincenzo, primary, and Hemminki, Akseli, primary

Published
2023
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27. Supplementary Figure 4 from Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, primary, Hirvinen, Mari L.M., primary, Escutenaire, Sophie, primary, Ugolini, Matteo, primary, Pesonen, Saila K., primary, Bramante, Simona, primary, Parviainen, Suvi, primary, Kanerva, Anna, primary, Loskog, Angelica S.I., primary, Eliopoulos, Aristides G., primary, Pesonen, Sari, primary, and Hemminki, Akseli, primary

Published
2023
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30. Treatment of Cancer Patients With a Serotype 5/3 Chimeric Oncolytic Adenovirus Expressing GMCSF

Author

Koski, Anniina, Kangasniemi, Lotta, Escutenaire, Sophie, Pesonen, Sari, Cerullo, Vincenzo, Diaconu, Iulia, Nokisalmi, Petri, Raki, Mari, Rajecki, Maria, Guse, Kilian, Ranki, Tuuli, Oksanen, Minna, Holm, Sirkka-Liisa, Haavisto, Elina, Karioja-Kallio, Aila, Laasonen, Leena, Partanen, Kaarina, Ugolini, Matteo, Helminen, Andreas, Karli, Eerika, Hannuksela, Päivi, Pesonen, Saila, Joensuu, Timo, Kanerva, Anna, and Hemminki, Akseli

Published
2010
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32. Nanofibrillated cellulose causes acute pulmonary inflammation that subsides within a month

Author

Ilves, Marit, primary, Vilske, Sara, additional, Aimonen, Kukka, additional, Lindberg, Hanna K., additional, Pesonen, Saila, additional, Wedin, Irene, additional, Nuopponen, Markus, additional, Vanhala, Esa, additional, Højgaard, Casper, additional, Winther, Jakob R., additional, Willemoës, Martin, additional, Vogel, Ulla, additional, Wolff, Henrik, additional, Norppa, Hannu, additional, Savolainen, Kai, additional, and Alenius, Harri, additional

Published
2018
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33. Nanofibrillated cellulose causes acute pulmonary inflammation that subsides within a month

Author

Ilves, Marit, Vilske, Sara, Aimonen, Kukka, Lindberg, Hanna K., Pesonen, Saila, Wedin, Irene, Nuopponen, Markus, Vanhala, Esa, Højgaard, Casper, Winther, Jakob R., Willemoës, Martin, Vogel, Ulla, Wolff, Henrik, Norppa, Hannu, Savolainen, Kai, Alenius, Harri, Ilves, Marit, Vilske, Sara, Aimonen, Kukka, Lindberg, Hanna K., Pesonen, Saila, Wedin, Irene, Nuopponen, Markus, Vanhala, Esa, Højgaard, Casper, Winther, Jakob R., Willemoës, Martin, Vogel, Ulla, Wolff, Henrik, Norppa, Hannu, Savolainen, Kai, and Alenius, Harri

Abstract

Nanofibrillated cellulose (NFC) is a renewable nanomaterial that has beneficial uses in various applications such as packaging materials and paper. Like carbon nanotubes (CNT), NFCs have high aspect ratio and favorable mechanical properties. The aspect ratio also rises a concern whether NFC could pose a health risk and induce pathologies, similar to those triggered by multi-walled CNT. In this study, we explored the immunomodulatory properties of four NFCs in vitro and in vivo, and compared the results with data on bulk-sized cellulose fibrils and rigid multi-walled CNT (rCNT). Two of the NFCs were non-functionalized and two were carboxymethylated or carboxylated. We investigated the production of pro-inflammatory cytokines in differentiated THP-1 cells, and studied the pulmonary effects and biopersistence of the materials in mice. Our results demonstrate that one of the non-functionalized NFCs tested reduced cell viability and triggered pro-inflammatory reactions in vitro. In contrast, all cellulose materials induced innate immunity response in vivo 24 h after oropharyngeal aspiration, and the non-functionalized NFCs additionally caused features of Th2-type inflammation. Modest immune reactions were also seen after 28 days, however, the effects were markedly attenuated as compared with the ones after 24 h. Cellulose materials were not cleared within 1 month, as demonstrated by their presence in the exposed lungs. All effects of NFC were modest as compared with those induced by rCNT. NFC-induced responses were similar or exceeded those triggered by bulk-sized cellulose. These data provide new information about the biodurability and pulmonary effects of different NFCs; this knowledge can be useful in the risk assessment of cellulose materials.

Published
2018

35. Fc-gamma receptor polymorphisms as predictive and prognostic factors in patients receiving oncolytic adenovirus treatment

Author

University of Helsinki, Faculty of Pharmacy, University of Helsinki, Haartman Institute, University of Helsinki, Dep. of Oncology (Institute of Clinical Medicine) (-2009), University of Helsinki, Clinicum, Hirvinen, Mari, Heiskanen, Raita, Oksanen, Minna, Pesonen, Saila, Liikanen, Ilkka, Joensuu, Timo, Kanerva, Anna, Cerullo, Vincenzo, Hemminki, Akseli, University of Helsinki, Faculty of Pharmacy, University of Helsinki, Haartman Institute, University of Helsinki, Dep. of Oncology (Institute of Clinical Medicine) (-2009), University of Helsinki, Clinicum, Hirvinen, Mari, Heiskanen, Raita, Oksanen, Minna, Pesonen, Saila, Liikanen, Ilkka, Joensuu, Timo, Kanerva, Anna, Cerullo, Vincenzo, and Hemminki, Akseli

Published
2013

36. Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, Cerullo, Vincenzo, Hirvinen, Mari L M, Escutenaire, Sophie, Ugolini, Matteo, Pesonen, Saila K, Bramante, Simona, Parviainen, Suvi, Kanerva, Anna, Loskog, Angelica S I, Eliopoulos, Aristides G, Pesonen, Sari, Hemminki, Akseli, Diaconu, Iulia, Cerullo, Vincenzo, Hirvinen, Mari L M, Escutenaire, Sophie, Ugolini, Matteo, Pesonen, Saila K, Bramante, Simona, Parviainen, Suvi, Kanerva, Anna, Loskog, Angelica S I, Eliopoulos, Aristides G, Pesonen, Sari, and Hemminki, Akseli

Abstract

Oncolytic adenovirus is an attractive platform for immunotherapy because virus replication is highly immunogenic and not subject to tolerance. Although oncolysis releases tumor epitopes and provides costimulatory danger signals, arming the virus with immunostimulatory molecules can further improve efficacy. CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several immune mechanisms, including a T-helper type 1 (TH1) response, which leads to activation of cytotoxic T cells and reduction of immunosuppression. In this study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3-hTERT-E1A-hCD40L)–mediated oncolysis resulted in enhanced calreticulin exposure and HMGB1 and ATP release, which were suggestive of immunogenicity. In two syngeneic mouse models, murine CD40L induced recruitment and activation of antigen-presenting cells, leading to increased interleukin-12 production in splenocytes. This effect was associated with induction of the TH1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L also displayed an enhanced presence of macrophages and cytotoxic CD8+ T cells but not B cells. Together, our findings show that adenoviruses coding for CD40L mediate multiple antitumor effects including oncolysis, apoptosis, induction of T-cell responses, and upregulation of TH1 cytokines.

Published
2012
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38. Antiviral and Antitumor T-cell Immunity in Patients Treated with GM-CSF–Coding Oncolytic Adenovirus

Author

Kanerva, Anna, primary, Nokisalmi, Petri, additional, Diaconu, Iulia, additional, Koski, Anniina, additional, Cerullo, Vincenzo, additional, Liikanen, Ilkka, additional, Tähtinen, Siri, additional, Oksanen, Minna, additional, Heiskanen, Raita, additional, Pesonen, Saila, additional, Joensuu, Timo, additional, Alanko, Tuomo, additional, Partanen, Kaarina, additional, Laasonen, Leena, additional, Kairemo, Kalevi, additional, Pesonen, Sari, additional, Kangasniemi, Lotta, additional, and Hemminki, Akseli, additional

Published
2013
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39. Abstract 3304: Oncolytic adenovirus with low-dose temozolomide induces autophagy and antitumor immune responses preclinically and in cancer patients.

Author

Liikanen, Ilkka, primary, Ahtiainen, Laura, additional, Hirvinen, Mari L.M, additional, Barmante, Simona, additional, Cerullo, Vincenzo, additional, Nokisalmi, Petri, additional, Hemminki, Otto, additional, Diaconu, Iulia, additional, Pesonen, Sari, additional, Koski, Anniina, additional, Kangasniemi, Lotta, additional, Pesonen, Saila K., additional, Oksanen, Minna, additional, Zhao, Fang, additional, Laasonen, Leena, additional, Partanen, Kaarina, additional, Joensuu, Timo, additional, Kanerva, Anna, additional, and Hemminki, Akseli, additional

Published
2013
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40. Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus

Author

Diaconu, Iulia, primary, Cerullo, Vincenzo, additional, Hirvinen, Mari L.M., additional, Escutenaire, Sophie, additional, Ugolini, Matteo, additional, Pesonen, Saila K., additional, Bramante, Simona, additional, Parviainen, Suvi, additional, Kanerva, Anna, additional, Loskog, Angelica S.I., additional, Eliopoulos, Aristides G., additional, Pesonen, Sari, additional, and Hemminki, Akseli, additional

Published
2012
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41. Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Pesonen, Sari, primary, Diaconu, Iulia, additional, Kangasniemi, Lotta, additional, Ranki, Tuuli, additional, Kanerva, Anna, additional, Pesonen, Saila K., additional, Gerdemann, Ulrike, additional, Leen, Ann M., additional, Kairemo, Kalevi, additional, Oksanen, Minna, additional, Haavisto, Elina, additional, Holm, Sirkka-Liisa, additional, Karioja-Kallio, Aila, additional, Kauppinen, Satu, additional, Partanen, Kaarina P. L., additional, Laasonen, Leena, additional, Joensuu, Tima, additional, Alanko, Tuomo, additional, Cerullo, Vincenzo, additional, and Hemminki, Akseli, additional

Published
2012
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42. Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

Author

Iulia Diaconu, Vincenzo Cerullo, Tuuli Ranki, Ulrike Gerdemann, Kaarina Partanen, T. Joensuu, Akseli Hemminki, Leena Laasonen, Ann M. Leen, Kalevi Kairemo, Aila Karioja-Kallio, Lotta Kangasniemi, Minna Oksanen, Sari Pesonen, Elina Haavisto, Sirkka-Liisa Holm, Satu Kauppinen, Saila K. Pesonen, Anna Kanerva, Tuomo Alanko, Pesonen, Sari, Diaconu, Iulia, Kangasniemi, Lotta, Ranki, Tuuli, Kanerva, Anna, Pesonen, Saila K., Gerdemann, Ulrike, Leen, Ann M., Kairemo, Kalevi, Oksanen, Minna, Haavisto, Elina, Holm, Sirkka-Liisa, Karioja-Kallio, Aila, Kauppinen, Satu, Partanen, Kaarina P. L., Laasonen, Leena, Joensuu, Tima, Alanko, Tuomo, Cerullo, Vincenzo, and Hemminki, Akseli

Subjects
Adult, Male, Cancer Research, medicine.medical_treatment, Genetic enhancement, CD40 Ligand, Antibodies, Viral, medicine.disease_cause, Multimodal Imaging, Peripheral blood mononuclear cell, Virus, Adenoviridae, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Humans, Medicine, Virotherapy, Chemokine CCL5, Telomerase, 030304 developmental biology, Oncolytic Virotherapy, 0303 health sciences, business.industry, ELISPOT, Virion, Immunotherapy, Th1 Cells, Middle Aged, 3. Good health, Oncolytic virus, Th1 Cell, Oncology, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Immunology, Neoplasm, Female, Tomography, X-Ray Computed, business, Human
Abstract

The immunosuppressive environment of advanced tumors is a primary obstacle to the efficacy of immunostimulatory and vaccine approaches. Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients. A double-targeted chimeric adenovirus controlled by the hTERT promoter and expressing CD40L (CGTG-401) was constructed and nine patients with progressing advanced solid tumors refractory to standard therapies were treated intratumorally. No serious adverse events resulting in patient hospitalization occurred. Moderate or no increases in neutralizing antibodies were seen, suggesting effective Th1 immunologic effects. An assessment of the blood levels of virus indicated 17.5% of the samples (n = 40) were positive at a low level early after treatment, but not thereafter. In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor. Peripheral blood mononuclear cells were analyzed by IFN-γ ELISPOT analysis and induction of both survivin-specific and adenovirus-specific T cells was seen. Antitumor T-cell responses were even more pronounced when assessed by intracellular cytokine staining after stimulation with tumor type–specific peptide pools. Of the evaluable patients, 83% displayed disease control at 3 months and in both cases in which treatment was continued the effect was sustained for at least 8 months. Injected and noninjected lesions responded identically. Together, these findings support further clinical evaluation of CGTG-401. Cancer Res; 72(7); 1621–31. ©2012 AACR.

Published
2012
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43. Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans

Author

Bramante, S, Koski, A, Kipar, A, Diaconu, I, Liikanen, I, Hemminki, O, Vassilev, L, Parviainen, S, Cerullo, V, Pesonen, S K, Oksanen, M, Heiskanen, R, Rouvinen-Lagerström, N, Merisalo-Soikkeli, M, Hakonen, T, Joensuu, T, Kanerva, A, Pesonen, S, Hemminki, A, Bramante, Simona, Koski, Anniina, Kipar, Anja, Diaconu, Iulia, Liikanen, Ilkka, Hemminki, Otto, Vassilev, Lotta, Parviainen, Suvi, Cerullo, Vincenzo, Pesonen, Saila K, Oksanen, Minna, Heiskanen, Raita, Rouvinen-Lagerström, Noora, Merisalo-Soikkeli, Maiju, Hakonen, Tiina, Joensuu, Timo, Kanerva, Anna, Pesonen, Sari, Hemminki, Akseli, University of Zurich, and Hemminki, A

Subjects
Cancer Research, Xenograft Model Antitumor Assay, Prognosi, 10184 Institute of Veterinary Pathology, Mice, Nude, Injections, Intralesional, Virus Replication, Animal models of cancer, Adenoviridae, Mice, Tumor Cells, Cultured, 1306 Cancer Research, Oncolytic Virotherapy, Mesocricetu, Cancer gene therapy, Animal, Granulocyte-Macrophage Colony-Stimulating Factor, GM-CSF, Sarcoma, Genetic Therapy, Survival Rate, Oncolytic adenoviru, Oncology, 570 Life sciences, biology, 2730 Oncology, Female, Human
Abstract

Sarcomas are a relatively rare cancer, but often incurable at the late metastatic stage. Oncolytic immunotherapy has gained attention over the past years, and a wide range of oncolytic viruses have been delivered via intratumoral injection with positive safety and promising efficacy data. Here, we report preclinical and clinical results from treatment of sarcoma with oncolytic adenovirus Ad5/3-D24-GMCSF (CGTG-102). Ad5/3-D24-GMCSF is a serotype chimeric oncolytic adenovirus coding for human granulocyte-macrophage colony-stimulating factor (GM-CSF). The efficacy of Ad5/3-D24-GMCSF was evaluated on a panel of soft-tissue sarcoma (STS) cell lines and in two animal models. Sarcoma specific human data were also collected from the Advanced Therapy Access Program (ATAP), in preparation for further clinical development. Efficacy was seen in both in vitro and in vivo STS models. Fifteen patients with treatment-refractory STS (13/15) or primary bone sarcoma (2/15) were treated in ATAP, and treatments appeared safe and well-tolerated. A total of 12 radiological RECIST response evaluations were performed, and two cases of minor response, six cases of stable disease and four cases of progressive disease were detected in patients progressing prior to virus treatment. Overall, the median survival time post treatment was 170 days. One patient is still alive at 1,459 days post virus treatment. In summary, Ad5/3-D24-GMCSF appears promising for the treatment of advanced STS; a clinical trial for treatment of refractory injectable solid tumors including STS is ongoing.

Published
2014

44. Fc-gamma receptor polymorphisms as predictive and prognostic factors in patients receiving oncolytic adenovirus treatment

Author

Saila K. Pesonen, Vincenzo Cerullo, Raita Heiskanen, Akseli Hemminki, Mari Hirvinen, Timo Joensuu, Minna Oksanen, Anna Kanerva, Ilkka Liikanen, Hirvinen, Mari, Heiskanen, Raita, Oksanen, Minna, Pesonen, Saila, Liikanen, Ilkka, Joensuu, Timo, Kanerva, Anna, Cerullo, Vincenzo, Hemminki, Akseli, Faculty of Pharmacy, Haartman Institute (-2014), Division of Biopharmaceutics and Pharmacokinetics (-2018), Transplantation Laboratory, Department of Pathology, Translational Cancer Biology (TCB) Research Programme, Research Programs Unit, Department of Obstetrics and Gynecology, Division of Pharmaceutical Biosciences, and ImmunoViroTherapy Lab

Subjects
Male, Oncolytic virus, medicine.medical_treatment, SUSCEPTIBILITY, medicine.disease_cause, Fc gamma receptor (FcgR), 0302 clinical medicine, Gene Frequency, CD40L, IDIOTYPE VACCINATION, Child, Medicine(all), Aged, 80 and over, Oncolytic Virotherapy, 0303 health sciences, Medicine (all), General Medicine, Middle Aged, Prognosis, Tumor antigen, CETUXIMAB, 3. Good health, Treatment Outcome, Child, Preschool, Female, Survival Analysi, Human, Oncolytic adenovirus, Adult, Adolescent, Genotype, Prognosi, education, Context (language use), Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Adenoviridae, 03 medical and health sciences, Young Adult, medicine, Humans, IGG-FC, BREAST-CANCER, NK cell, IMMUNOTHERAPY, Survival analysis, 030304 developmental biology, Aged, Biochemistry, Genetics and Molecular Biology (all), business.industry, Biochemistry, Genetics and Molecular Biology(all), Research, R POLYMORPHISMS, Receptors, IgG, Cancer, Oncolytic viru, GM-CSF, Immunotherapy, medicine.disease, Survival Analysis, METASTATIC COLORECTAL-CANCER, HUMORAL IMMUNE-RESPONSE, Immunology, 3111 Biomedicine, business, 030215 immunology
Abstract

Background Oncolytic viruses have shown potential as cancer therapeutics, but not all patients seem to benefit from therapy. Polymorphisms in Fc gamma receptors (FcgRs) lead to altered binding affinity of IgG between the receptor allotypes and therefore contribute to differences in immune defense mechanisms. Associations have been identified between FcgR polymorphisms and responsiveness to different immunotherapies. Taken together with the increasing understanding that immunological factors might determine the efficacy of oncolytic virotherapy we studied whether FcgR polymorphisms would have prognostic and/or predictive significance in the context of oncolytic adenovirus treatments. Methods 235 patients with advanced solid tumors were genotyped for two FcgR polymorphisms, FcgRIIa-H131R (rs1801274) and FcgRIIIa-V158F (rs396991), using TaqMan based qPCR. The genotypes were correlated with patient survival and tumor imaging data. Results In patients treated with oncolytic adenoviruses, overall survival was significantly shorter if the patient had an FcgRIIIa-VV/ FcgRIIa-HR (VVHR) genotype combination (P = 0,032). In contrast, patients with FFHR and FFRR genotypes had significantly longer overall survival (P = 0,004 and P = 0,006, respectively) if they were treated with GM-CSF-armed adenovirus in comparison to other viruses. Treatment of these patients with unarmed virus correlated with shorter survival (P Conclusions Our data are compatible with the hypothesis that individual differences in effector cell functions, such as NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and tumor antigen presentation by APCs caused by polymorphisms in FcgRs could play role in the effectiveness of oncolytic virotherapies. If confirmed in larger populations, FcgR polymorphisms could have potential as prognostic and predictive biomarkers for oncolytic adenovirus therapies to enable better selection of patients for clinical trials. Also, putative associations between genotypes, different viruses and survival implicate potentially important mechanistic issues.

Published
2013

45. Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus

Author

Saila K. Pesonen, Ilkka Liikanen, Vincenzo Cerullo, Leena Laasonen, Lotta Kangasniemi, Petri Nokisalmi, Tuomo Alanko, Anna Kanerva, Anniina Koski, Iulia Diaconu, T. Joensuu, Minna Oksanen, Kalevi Kairemo, Raita Heiskanen, Akseli Hemminki, Sari Pesonen, Siri Tähtinen, K. Partanen, Kanerva, Anna, Nokisalmi, Petri, Diaconu, Iulia, Koski, Anniina, Cerullo, Vincenzo, Liikanen, Ilkka, Tähtinen, Siri, Oksanen, Minna, Heiskanen, Raita, Pesonen, Saila, Joensuu, Timo, Alanko, Tuomo, Partanen, Kaarina, Laasonen, Leena, Kairemo, Kalevi, Pesonen, Sari, Kangasniemi, Lotta, and Hemminki, Akseli

Subjects
Oncolytic adenovirus, Adult, Male, Cancer Research, Adolescent, Time Factor, medicine.medical_treatment, Enzyme-Linked Immunosorbent Assay, Oncolytic Viruse, Virus, Adenoviridae, 03 medical and health sciences, Interferon-gamma, Young Adult, 0302 clinical medicine, Cancer immunotherapy, Immunity, Medicine, Macrophage, Child, Immunologic Tolerance, 030304 developmental biology, Aged, Clonal Anergy, Oncolytic Virotherapy, 0303 health sciences, biology, business.industry, Tumor Necrosis Factor-alpha, Medicine (all), Granulocyte-Macrophage Colony-Stimulating Factor, Middle Aged, Capsid Protein, 3. Good health, Oncolytic virus, Interleukin-10, Treatment Outcome, T-Lymphocyte, Oncology, 030220 oncology & carcinogenesis, Immunology, biology.protein, Neoplasm, Female, Survival Analysi, Antibody, business, Human
Abstract

Purpose: Multiple injections of oncolytic adenovirus could enhance immunologic response. In the first part of this article, the focus was on immunologic aspects. Sixty patients previously naïve to oncolytic virus and who had white blood cells available were treated. Thirty-nine of 60 were assessed after a single virus administration, whereas 21 of 60 received a “serial treatment” consisting of three injections within 10 weeks. In the second part, we focused on 115 patients treated with a granulocyte macrophage colony-stimulating factor (GM–CSF)–coding capsid chimeric adenovirus, CGTG-102. Results: Following serial treatment, both increase and decrease in antitumor T cells in blood were seen more frequently, findings which are compatible with induction of T-cell immunity and trafficking of T cells to tumors, respectively. Safety was good in both groups. In 115 patients treated with CGTG-102 (Ad5/3-D24-GMCSF), median overall survival was 111 days following single and 277 days after serial treatment in nonrandomized comparison. Switching the virus capsid for avoiding neutralizing antibodies in a serial treatment featuring three different viruses did not impact safety or efficacy. A correlation between antiviral and antitumor T cells was seen (P = 0.001), suggesting that viral oncolysis can result in epitope spreading and breaking of tumor-associated immunologic tolerance. Alternatively, some patients may be more susceptible to induction of T-cell immunity and/or trafficking. Conclusions: These results provide the first human data linking antiviral immunity with antitumor immunity, implying that oncolytic viruses could have an important role in cancer immunotherapy. Clin Cancer Res; 19(10); 2734–44. ©2013 AACR.

Published
2013

46. Immune response is an important aspect of the antitumor effect produced by a CD40L-encoding oncolytic adenovirus

Author

Akseli Hemminki, Angelica Loskog, Saila K. Pesonen, Simona Bramante, Suvi Parviainen, Iulia Diaconu, A. Kanerva, Aristides G. Eliopoulos, Matteo Ugolini, Sophie Escutenaire, Sari Pesonen, Mari Hirvinen, Vincenzo Cerullo, Diaconu, Iulia, Cerullo, Vincenzo, Hirvinen, Mari L. M., Escutenaire, Sophie, Ugolini, Matteo, Pesonen, Saila K., Bramante, Simona, Parviainen, Suvi, Kanerva, Anna, Loskog, Angelica S. I., Eliopoulos, Aristides G., Pesonen, Sari, and Hemminki, Akseli

Subjects
Oncolytic adenovirus, Cancer Research, Xenograft Model Antitumor Assay, Genetic enhancement, CD40 Ligand, Melanoma, Experimental, Mice, Nude, chemical and pharmacologic phenomena, Apoptosis, Oncolytic Viruse, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Neoplasms, Cell Line, Tumor, Cytotoxic T cell, Medicine, Animals, Humans, CD154, Cytokine, 030304 developmental biology, Oncolytic Virotherapy, 0303 health sciences, CD40, biology, business.industry, Animal, Apoptosi, T-Lymphocytes, Helper-Inducer, Virology, Tumor site, Xenograft Model Antitumor Assays, 3. Good health, Mice, Inbred C57BL, Oncolytic Viruses, Urinary Bladder Neoplasms, Oncology, 030220 oncology & carcinogenesis, Urinary Bladder Neoplasm, biology.protein, Ovarian cancer cells, Cytokines, Neoplasm, business, Human, T-Lymphocytes, Cytotoxic
Abstract

Oncolytic adenovirus is an attractive platform for immunotherapy because virus replication is highly immunogenic and not subject to tolerance. Although oncolysis releases tumor epitopes and provides costimulatory danger signals, arming the virus with immunostimulatory molecules can further improve efficacy. CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several immune mechanisms, including a T-helper type 1 (TH1) response, which leads to activation of cytotoxic T cells and reduction of immunosuppression. In this study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3-hTERT-E1A-hCD40L)–mediated oncolysis resulted in enhanced calreticulin exposure and HMGB1 and ATP release, which were suggestive of immunogenicity. In two syngeneic mouse models, murine CD40L induced recruitment and activation of antigen-presenting cells, leading to increased interleukin-12 production in splenocytes. This effect was associated with induction of the TH1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L also displayed an enhanced presence of macrophages and cytotoxic CD8+ T cells but not B cells. Together, our findings show that adenoviruses coding for CD40L mediate multiple antitumor effects including oncolysis, apoptosis, induction of T-cell responses, and upregulation of TH1 cytokines. Cancer Res; 72(9); 2327–38. ©2012 AACR.

Published
2012

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