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2. Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy

Author

Jonak Zdenka, Adams Sarah, Benencia Fabian, Carpenito Carmine, Tsiatas Marinos, Facciabene Andrea, Alagkiozidis Ioannis, June Carl H, Powell Daniel J, and Coukos George

Subjects
Medicine
Abstract

Abstract Background Time-dependent chemotherapeutic agents can selectively target tumor cells in susceptible phases of the cell cycle however a fraction of tumor cells in non-vulnerable cell cycle phases remain drug-resistant. Immunotherapy represents a promising approach to overcome the limitation of phase-specific drugs and improve their clinical efficacy. Here, we investigated the potential use of anticancer chemotherapeutic drugs in combination with IL-18, a cytokine with strong immunostimulatory properties. Methods Four chemotherapeutic drugs commonly used in ovarian cancer were first tested for the ability to increase the immunogenicity and killing of the murine ovarian cancer cell line ID8 in vitro. Chemotherapeutric agents with measured time-dependent immune-enhancing effects were then tested for antitumor effectiveness in vivo in combination with IL-18 immunotherapy using the ID8-Vegf ovarian cancer model. Results Paclitaxel or topotecan exposure alone mediated incomplete, time-dependent killing against the murine ovarian cancer cell line ID8 in vitro, whereas carboplatin or gemcitabine mediated comprehensive, dose-dependent killing. In the plateau phase of the time-dependent killing by topotecan or paclitaxel, drug-resistant ID8 cells were more immunogenic with elevated expression of MHC-I and Fas, and increased sensitivity to CTL and Fas agonistic antibody in vitro. Moreover, the antitumor effectiveness of time-dependent agents in vivo was significantly improved with the addition of IL-18 through a T cell-dependent mechanism, while the effectiveness of drugs without significant phase specificity were not. Conclusions Tumor immunotherapy with IL-18 can significantly augment the killing fraction of phase-specific chemotherapeutic drugs and provide survival benefit. The safety profile of IL-18 and its positive interactions with select anticancer chemotherapeutic agents strongly supports the clinical investigation of this combinatorial approach.

Published
2011
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3. Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18

Author

Danet-Desnoyers Gwen-äel, Hammond Rachel, Gimotty Phyllis A, Carroll Richard G, Adams Sarah, Jonak Zdenka, Benencia Fabian, Carpenito Carmine, Facciabene Andrea, Alagkiozidis Ioannis, June Carl H, Powell Daniel J, and Coukos George

Subjects
Medicine
Abstract

Abstract Background Liposomal doxorubicin (Doxil) is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated. Methods Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack in vitro. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18), a pleiotropic immunostimulatory cytokine, was investigated in vivo in mice bearing ID8-Vegf tumors. Results While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death in vitro. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy in vivo and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice. Conclusion These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 in vivo.

Published
2009
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5. Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy

Author

Uribe-Herranz, Mireia, Beghi, Silvia, Ruella, Marco, Parvathaneni, Kalpana, Salaris, Silvano, Kostopoulos, Nektarios, George, Subin S., Pierini, Stefano, Krimitza, Elisavet, Costabile, Francesca, Ghilardi, Guido, Amelsberg, Kimberly V., Lee, Yong Gu, Pajarillo, Raymone, Markmann, Caroline, McGettigan-Croce, Bevin, Agarwal, Divyansh, Frey, Noelle, Lacey, Simon F., Scholler, John, Gabunia, Khatuna, Wu, Gary, Chong, Elise, Porter, David L., June, Carl H., Schuster, Stephen J., Bhoj, Vijay, and Facciabene, Andrea

Published
2023
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6. Author Correction: Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

Author

Smith, Melody, Dai, Anqi, Ghilardi, Guido, Amelsberg, Kimberly V., Devlin, Sean M., Pajarillo, Raymone, Slingerland, John B., Beghi, Silvia, Herrera, Pamela S., Giardina, Paul, Clurman, Annelie, Dwomoh, Emmanuel, Armijo, Gabriel, Gomes, Antonio L. C., Littmann, Eric R., Schluter, Jonas, Fontana, Emily, Taur, Ying, Park, Jae H., Palomba, Maria Lia, Halton, Elizabeth, Ruiz, Josel, Jain, Tania, Pennisi, Martina, Afuye, Aishat Olaide, Perales, Miguel-Angel, Freyer, Craig W., Garfall, Alfred, Gier, Shannon, Nasta, Sunita, Landsburg, Daniel, Gerson, James, Svoboda, Jakub, Cross, Justin, Chong, Elise A., Giralt, Sergio, Gill, Saar I., Riviere, Isabelle, Porter, David L., Schuster, Stephen J., Sadelain, Michel, Frey, Noelle, Brentjens, Renier J., June, Carl H., Pamer, Eric G., Peled, Jonathan U., Facciabene, Andrea, van den Brink, Marcel R. M., and Ruella, Marco

Published
2023
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7. Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

Author

Smith, Melody, Dai, Anqi, Ghilardi, Guido, Amelsberg, Kimberly V., Devlin, Sean M., Pajarillo, Raymone, Slingerland, John B., Beghi, Silvia, Herrera, Pamela S., Giardina, Paul, Clurman, Annelie, Dwomoh, Emmanuel, Armijo, Gabriel, Gomes, Antonio L. C., Littmann, Eric R., Schluter, Jonas, Fontana, Emily, Taur, Ying, Park, Jae H., Palomba, Maria Lia, Halton, Elizabeth, Ruiz, Josel, Jain, Tania, Pennisi, Martina, Afuye, Aishat Olaide, Perales, Miguel-Angel, Freyer, Craig W., Garfall, Alfred, Gier, Shannon, Nasta, Sunita, Landsburg, Daniel, Gerson, James, Svoboda, Jakub, Cross, Justin, Chong, Elise A., Giralt, Sergio, Gill, Saar I., Riviere, Isabelle, Porter, David L., Schuster, Stephen J., Sadelain, Michel, Frey, Noelle, Brentjens, Renier J., June, Carl H., Pamer, Eric G., Peled, Jonathan U., Facciabene, Andrea, van den Brink, Marcel R. M., and Ruella, Marco

Published
2022
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12. Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response

Author

Uribe-Herranz, Mireia, Rafail, Stavros, Beghi, Silvia, Gil-de-Gomez, Luis, Verginadis, Ioannis, Bittinger, Kyle, Pustylnikov, Sergey, Pierini, Stefano, Perales-Linares, Renzo, Blair, Ian A., Mesaros, Clementina A., Snyder, Nathaniel W., Bushman, Frederic, Koumenis, Constantinos, and Facciabene, Andrea

Subjects
Thermo Fisher Scientific Inc., University of Pennsylvania, Cancer treatment, Antigens, Microbiota (Symbiotic organisms), Tumors, Radiotherapy, Dendritic cells, Immune response, Antibacterial agents, Scientific equipment industry, T cells, Antibiotics, Cancer, Esters, Vancomycin, Diseases, Bacteria, Metabolites
Abstract

Introduction Radiotherapy (RT) is a well-established antitumor treatment, with more than 50% of newly diagnosed cancer patients with solid tumors receiving RT at some point during their treatment, usually in [...], Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor- associated antigen (TAA) cross-priming with antitumor [CD8.sup.+] T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteria and is restricted to the gut, potentiated the RT-induced antitumor immune response and tumor growth inhibition. This synergy was dependent on TAA cross presentation to cytolytic [CD8.sup.+] T cells and on IFN-[gamma]. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, depletion of vancomycin-sensitive bacteria enhances the antitumor activity of RT, which has important clinical ramifications.

Published
2020
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14. Rapid tumor vaccine using Toll-like receptor-activated ovarian cancer ascites monocytes

Author

George Coukos, Andrea Facciabene, Lana E Kandalaft, Christopher Neal, Dallas Flies, Justine Michaux, HuiSong Pak, Michal Bassani-Sternberg, Sarah F Adams, Sylvie Rusakiewicz, Georgia A McCann, Alizée J Grimm, Cheryl L-L Chiang, Ananda Mookerjee, Stephanie Jean, Florian Huber, Denarda Dangaj, and Phyllis A Gimotty

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Novel therapeutic strategies in ovarian cancer (OC) are needed as the survival rate remains dismally low. Although dendritic cell-based cancer vaccines are effective in eliciting therapeutic responses, their complex and costly manufacturing process hampers their full clinical utility outside specialized clinics. Here, we describe a novel approach of generating a rapid and effective cancer vaccine using ascites-derived monocytes for treating OC.Methods Using the ID8 mouse ovarian tumor model and OC patient samples, we isolated ascites monocytes and evaluated them with flow cytometry, Luminex cytokine and chemokine array analysis, ex vivo cocultures with T cells, in vivo tumor challenge and T cell transfer experiments, RNA-sequencing and mass spectrometry.Results We demonstrated the feasibility of isolating ascites monocytes and restoring their ability to function as bona fide antigen-presenting cells (APCs) with Toll-like receptor (TLR) 4 lipopolysaccharide and TLR9 CpG-oligonucleotides, and a blocking antibody to interleukin-10 receptor (IL-10R Ab) in the ID8 model. The ascites monocytes were laden with tumor antigens at a steady state in vivo. After a short 48 hours activation, they upregulated maturation markers (CD80, CD86 and MHC class I) and demonstrated strong ex vivo T cell stimulatory potential and effectively suppressed tumor and malignant ascites in vivo. They also induced protective long-term T cell memory responses. To evaluate the translational potential of this approach, we isolated ascites monocytes from stage III/IV chemotherapy-naïve OC patients. Similarly, the human ascites monocytes presented tumor-associated antigens (TAAs), including MUC1, ERBB2, mesothelin, MAGE, PRAME, GPC3, PMEL and TP53 at a steady state. After a 48-hour treatment with TLR4 and IL-10R Ab, they efficiently stimulated oligoclonal tumor-associated lymphocytes (TALs) with strong reactivity against TAAs. Importantly, the activated ascites monocytes retained their ability to activate TALs in the presence of ascitic fluid.Conclusions Ascites monocytes are naturally loaded with tumor antigen and can perform as potent APCs following short ex vivo activation. This novel ascites APC vaccine can be rapidly prepared in 48 hours with a straightforward and affordable manufacturing process, and would be an attractive therapeutic vaccine for OC.

Published
2020
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15. Supplementary Table 1 - Gene Expression from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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16. Supp. Figure 2 from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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17. Supp. Figure 6 from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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18. Data from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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19. Supp. Figure 4 from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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20. Supp. Figure 1 from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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21. Supplementary Figure Legends from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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22. Supp. Figure 3 from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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23. Supp. Figure 5 from Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, primary, Mohei, Hesham, primary, Beghi, Silvia, primary, Rivera, Osvaldo D., primary, Kostopoulos, Nektarios, primary, Giglio, Andrea, primary, George, Subin S., primary, Uribe-Herranz, Mireia, primary, Costabile, Francesca, primary, Pierini, Stefano, primary, Pustylnikov, Sergei, primary, Skoufos, Giorgos, primary, Barash, Yoseph, primary, Hatzigeorgiou, Artemis G., primary, Koumenis, Constantinos, primary, Maity, Amit, primary, Lotze, Michael T., primary, and Facciabene, Andrea, primary

Published
2023
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25. Parkin Deficiency Suppresses Antigen Presentation to Promote Tumor Immune Evasion and Immunotherapy Resistance

Author

Perales-Linares, Renzo, primary, Leli, Nektaria Maria, additional, Mohei, Hesham, additional, Beghi, Silvia, additional, Rivera, Osvaldo D., additional, Kostopoulos, Nektarios, additional, Giglio, Andrea, additional, George, Subin S., additional, Uribe-Herranz, Mireia, additional, Costabile, Francesca, additional, Pierini, Stefano, additional, Pustylnikov, Sergei, additional, Skoufos, Giorgos, additional, Barash, Yoseph, additional, Hatzigeorgiou, Artemis G., additional, Koumenis, Constantinos, additional, Maity, Amit, additional, Lotze, Michael T., additional, and Facciabene, Andrea, additional

Published
2023
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26. Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy, But Not Combination Therapy

Author

Emily J Anstadt, Brian Chu, Nikhil Yegya-Raman, Xiaoyan Han, Abigail Doucette, Kendra Poirier, Jahan J Mohiuddin, Amit Maity, Andrea Facciabene, Ravi K Amaravadi, Giorgos C Karakousis, Justine V Cohen, Tara C Mitchell, Lynn M Schuchter, and John N Lukens

Subjects
Cancer Research, Oncology, Humans, Steroids, Colitis, Ipilimumab, Melanoma, Retrospective Studies
Abstract

Background For patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making. Materials and Methods Patients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS). Results In total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS. Conclusion This single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.

Published
2022
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29. Data from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

Monk, Bradley J., primary, Facciabene, Andrea, primary, Brady, William E., primary, Aghajanian, Carol A., primary, Fracasso, Paula M., primary, Walker, Joan L., primary, Lankes, Heather A., primary, Manjarrez, Kristi L., primary, Danet-Desnoyers, Gwenn-äel H., primary, Bell-McGuinn, Katherine M., primary, McCourt, Carolyn K., primary, Malykhin, Alexander, primary, Hershberg, Robert M., primary, and Coukos, George, primary

Published
2023
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30. Supplemental Tables from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

Monk, Bradley J., primary, Facciabene, Andrea, primary, Brady, William E., primary, Aghajanian, Carol A., primary, Fracasso, Paula M., primary, Walker, Joan L., primary, Lankes, Heather A., primary, Manjarrez, Kristi L., primary, Danet-Desnoyers, Gwenn-äel H., primary, Bell-McGuinn, Katherine M., primary, McCourt, Carolyn K., primary, Malykhin, Alexander, primary, Hershberg, Robert M., primary, and Coukos, George, primary

Published
2023
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31. Supplemental Figures from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

Monk, Bradley J., primary, Facciabene, Andrea, primary, Brady, William E., primary, Aghajanian, Carol A., primary, Fracasso, Paula M., primary, Walker, Joan L., primary, Lankes, Heather A., primary, Manjarrez, Kristi L., primary, Danet-Desnoyers, Gwenn-äel H., primary, Bell-McGuinn, Katherine M., primary, McCourt, Carolyn K., primary, Malykhin, Alexander, primary, Hershberg, Robert M., primary, and Coukos, George, primary

Published
2023
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32. Supplemental Figure Legends from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

Monk, Bradley J., primary, Facciabene, Andrea, primary, Brady, William E., primary, Aghajanian, Carol A., primary, Fracasso, Paula M., primary, Walker, Joan L., primary, Lankes, Heather A., primary, Manjarrez, Kristi L., primary, Danet-Desnoyers, Gwenn-äel H., primary, Bell-McGuinn, Katherine M., primary, McCourt, Carolyn K., primary, Malykhin, Alexander, primary, Hershberg, Robert M., primary, and Coukos, George, primary

Published
2023
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33. Supplemental Methods from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

Monk, Bradley J., primary, Facciabene, Andrea, primary, Brady, William E., primary, Aghajanian, Carol A., primary, Fracasso, Paula M., primary, Walker, Joan L., primary, Lankes, Heather A., primary, Manjarrez, Kristi L., primary, Danet-Desnoyers, Gwenn-äel H., primary, Bell-McGuinn, Katherine M., primary, McCourt, Carolyn K., primary, Malykhin, Alexander, primary, Hershberg, Robert M., primary, and Coukos, George, primary

Published
2023
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36. Supplemental Figures from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

George Coukos, Robert M. Hershberg, Alexander Malykhin, Carolyn K. McCourt, Katherine M. Bell-McGuinn, Gwenn-äel H. Danet-Desnoyers, Kristi L. Manjarrez, Heather A. Lankes, Joan L. Walker, Paula M. Fracasso, Carol A. Aghajanian, William E. Brady, Andrea Facciabene, and Bradley J. Monk

Abstract

Supplemental Figure 1 Species-specific activation of TLR8 by motolimod. Supplemental Figure 2 Full human immune cell reconstitution in NSG-HIS mice. Supplemental Figure 3 Response to PLD + motolimod is not schedule-sensitive in the NSG-HIS mouse. Supplemental Figure 4 Assessment of macrophage-induced apoptosis using motolimod in combination with PLD. Supplemental Figure 5 Isolation of tumor-infiltrating T cells with specific tumor recognition and lysis ex vivo. Supplemental Figure 6 Pharmacokinetic (PK) evaluations. Supplemental Figure 7 Biological efficacy of motolimod in combination with paclitaxel.

Published
2023
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37. Supplemental Tables from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

Author

George Coukos, Robert M. Hershberg, Alexander Malykhin, Carolyn K. McCourt, Katherine M. Bell-McGuinn, Gwenn-äel H. Danet-Desnoyers, Kristi L. Manjarrez, Heather A. Lankes, Joan L. Walker, Paula M. Fracasso, Carol A. Aghajanian, William E. Brady, Andrea Facciabene, and Bradley J. Monk

Abstract

Table S1. Subject demographics and baseline characteristics Table S2. Tumor response as assessed by RECIST 1.1 and biochemical response

Published
2023
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40. Radiation Therapy for Bridging and Improving CAR-T Cell Therapy

Author

Kostopoulos, N., primary, Bedgi, S., additional, Krimitza, E., additional, Costabile, F., additional, Paydar, I., additional, Kim, M.M., additional, LaRiviere, M.J., additional, Maity, A., additional, Schuster, S., additional, Plastaras, J.P., additional, and Facciabene, A., additional

Published
2022
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41. 572 Gut microbiota tuning promotes tumor-associated antigen cross-presentation and enhances CAR T antitumor effects

Author

Facciabene, Andrea, primary, Uribe-Herranz, Mireia, additional, Beghi, Silvia, additional, Ruella, Marco, additional, Parvathaneni, Kalpana, additional, Ghilrardi, Guido, additional, Lee, Yung Gu, additional, Frey, Noelle, additional, Scholler, John, additional, Gabunia, Khatuna, additional, Specialist, Research, additional, Wu, Gary, additional, Chong, Elise, additional, Porter, David, additional, June, Carl, additional, Schuster, Stephen, additional, and Bhoj, Vijay, additional

Published
2022
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42. Author Correction: Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

Author

Smith, Melody, primary, Dai, Anqi, additional, Ghilardi, Guido, additional, Amelsberg, Kimberly V., additional, Devlin, Sean M., additional, Pajarillo, Raymone, additional, Slingerland, John B., additional, Beghi, Silvia, additional, Herrera, Pamela S., additional, Giardina, Paul, additional, Clurman, Annelie, additional, Dwomoh, Emmanuel, additional, Armijo, Gabriel, additional, Gomes, Antonio L. C., additional, Littmann, Eric R., additional, Schluter, Jonas, additional, Fontana, Emily, additional, Taur, Ying, additional, Park, Jae H., additional, Palomba, Maria Lia, additional, Halton, Elizabeth, additional, Ruiz, Josel, additional, Jain, Tania, additional, Pennisi, Martina, additional, Afuye, Aishat Olaide, additional, Perales, Miguel-Angel, additional, Freyer, Craig W., additional, Garfall, Alfred, additional, Gier, Shannon, additional, Nasta, Sunita, additional, Landsburg, Daniel, additional, Gerson, James, additional, Svoboda, Jakub, additional, Cross, Justin, additional, Chong, Elise A., additional, Giralt, Sergio, additional, Gill, Saar I., additional, Riviere, Isabelle, additional, Porter, David L., additional, Schuster, Stephen J., additional, Sadelain, Michel, additional, Frey, Noelle, additional, Brentjens, Renier J., additional, June, Carl H., additional, Pamer, Eric G., additional, Peled, Jonathan U., additional, Facciabene, Andrea, additional, van den Brink, Marcel R. M., additional, and Ruella, Marco, additional

Published
2022
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47. Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy, But Not Combination Therapy

Author

Anstadt, Emily J, primary, Chu, Brian, additional, Yegya-Raman, Nikhil, additional, Han, Xiaoyan, additional, Doucette, Abigail, additional, Poirier, Kendra, additional, Mohiuddin, Jahan J, additional, Maity, Amit, additional, Facciabene, Andrea, additional, Amaravadi, Ravi K, additional, Karakousis, Giorgos C, additional, Cohen, Justine V, additional, Mitchell, Tara C, additional, Schuchter, Lynn M, additional, and Lukens, John N, additional

Published
2022
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48. Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy

Author

Jacob E. Shabason, Cathy Zheng, Alexander Lin, Jahan J. Mohiuddin, Andrea Facciabene, Amit Maity, Alexander C. Huang, Wei Xu, John N. Lukens, Emily J. Anstadt, Samuel Swisher-McClure, Tara C. Mitchell, Brian Chu, Abigail Doucette, Lynn M. Schuchter, Xingmei Wang, Kendra Poirier, Giorgos C. Karakousis, and Ravi K. Amaravadi

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, medicine.drug_class, Antibiotics, Disease-Free Survival, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Internal medicine, Humans, Immunologic Factors, Medicine, Colitis, Immune Checkpoint Inhibitors, Melanoma, Aged, Neoplasm Staging, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Proportional hazards model, business.industry, Incidence (epidemiology), Hazard ratio, Genetic Variation, Cancer, Articles, Middle Aged, medicine.disease, Confidence interval, Anti-Bacterial Agents, Gastrointestinal Microbiome, Oncology, 030220 oncology & carcinogenesis, Toxicity, Female, Immunotherapy, business
Abstract

Background Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. Methods Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. Results There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P Conclusion Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.

Published
2020
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