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626 results on '"Sampson, John H"'

1. CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis

Author

Lerner, Emily C., Woroniecka, Karolina I., D’Anniballe, Vincent M., Wilkinson, Daniel S., Mohan, Aditya A., Lorrey, Selena J., Waibl-Polania, Jessica, Wachsmuth, Lucas P., Miggelbrink, Alexandra M., Jackson, Joshua D., Cui, Xiuyu, Raj, Jude A., Tomaszewski, William H., Cook, Sarah L., Sampson, John H., Patel, Anoop P., Khasraw, Mustafa, Gunn, Michael D., and Fecci, Peter E.

Published
2023
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6. Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy

Author

Gromeier, Matthias, Brown, Michael C., Zhang, Gao, Lin, Xiang, Chen, Yeqing, Wei, Zhi, Beaubier, Nike, Yan, Hai, He, Yiping, Desjardins, Annick, Herndon, II, James E., Varn, Frederick S., Verhaak, Roel G., Zhao, Junfei, Bolognesi, Dani P., Friedman, Allan H., Friedman, Henry S., McSherry, Frances, Muscat, Andrea M., Lipp, Eric S., Nair, Smita K., Khasraw, Mustafa, Peters, Katherine B., Randazzo, Dina, Sampson, John H., McLendon, Roger E., Bigner, Darell D., and Ashley, David M.

Published
2021
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8. Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses

Author

Huang, Min-Nung, Nicholson, Lowell T., Batich, Kristen A., Swartz, Adam M., Kopin, David, Wellford, Sebastian, Prabhakar, Vijay K., Woroniecka, Karolina, Nair, Smita K., Fecci, Peter E., Sampson, John H., and Gunn, Michael D.

Subjects
Antigens -- Analysis -- Health aspects, Cancer vaccines -- Analysis -- Health aspects, B cells -- Analysis -- Health aspects, Peptides -- Analysis -- Health aspects, Immunotherapy -- Analysis -- Health aspects, Dendritic cells -- Analysis -- Health aspects, T cells -- Analysis -- Health aspects, Vaccines, Lymphocytes, Gliomas, Cancer, Tumors, Glioblastomas, Medical tests, Health care industry
Abstract

Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, suggesting that exogenous DCs stimulate antitumor immunity by transferring antigens (Ags) to endogenous DCs. Such Ag transfer functions are most commonly ascribed to monocytes, implying that undifferentiated monocytes would function equally well as a vaccine modality and need not be differentiated to DCs to be effective. Here, we used several murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed antitumor activity superior to DC vaccines in several cancer models, including aggressive intracranial glioblastoma. Ag-loaded monocytes induced robust CTL responses via Ag transfer to splenic [CD8.sup.+] DCs in a manner independent of monocyte APC activity. Ag transfer required cell-cell contact and the formation of connexin 43- containing gap junctions between monocytes and DCs. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and [CD8.sup.+] DCs and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers., Introduction A major approach to cancer immunotherapy is the use of cellular vaccines to induce cytotoxic T lymphocyte (CTL) responses against specific tumor antigens (Ags) (1, 2). Among tumor vaccine [...]

Published
2020
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11. Challenges to curing primary brain tumours

Author

Aldape, Kenneth, Brindle, Kevin M., Chesler, Louis, Chopra, Rajesh, Gajjar, Amar, Gilbert, Mark R., Gottardo, Nicholas, Gutmann, David H., Hargrave, Darren, Holland, Eric C., Jones, David T. W., Joyce, Johanna A., Kearns, Pamela, Kieran, Mark W., Mellinghoff, Ingo K., Merchant, Melinda, Pfister, Stefan M., Pollard, Steven M., Ramaswamy, Vijay, Rich, Jeremy N., Robinson, Giles W., Rowitch, David H., Sampson, John H., Taylor, Michael D., Workman, Paul, and Gilbertson, Richard J.

Published
2019
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12. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors

Author

Chongsathidkiet, Pakawat, Jackson, Christina, Koyama, Shohei, Loebel, Franziska, Cui, Xiuyu, Farber, S. Harrison, Woroniecka, Karolina, Elsamadicy, Aladine A., Dechant, Cosette A., Kemeny, Hanna R., Sanchez-Perez, Luis, Cheema, Tooba A., Souders, Nicholas C., Herndon, James E., Coumans, Jean-Valery, Everitt, Jeffrey I., Nahed, Brian V., Sampson, John H., Gunn, Michael D., Martuza, Robert L., Dranoff, Glenn, Curry, William T., and Fecci, Peter E.

Published
2018
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13. Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study

Author

Mueller, Sabine, Polley, Mei-Yin, Lee, Benjamin, Kunwar, Sandeep, Pedain, Christoph, Wembacher-Schröder, Eva, Mittermeyer, Stephan, Westphal, Manfred, Sampson, John H., Vogelbaum, Michael A., Croteau, David, and Chang, Susan M.

Subjects
Medicine & Public Health, Neurology, Oncology, Convection enhanced delivery, PRECISE study, Imaging, Catheter scores, Recurrent glioblastoma
Abstract

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial.

Published
2011

17. Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

Author

Sampson, John H, Achrol, Achal Singh, Aghi, Manish K, Bankiewicz, Krystof, Bexon, Martin, Brem, Steven, Brenner, Andrew, Chandhasin, Chandtip, Chowdhary, Sajeel, Coello, Melissa, Ellingson, Benjamin M, Floyd, John R, Han, Seunggu, Kesari, Santosh, Mardor, Yael, Merchant, Fahar, Merchant, Nina, Randazzo, Dina, Vogelbaum, Michael, and Vrionis, Frank

Published
2023
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22. Reply to ‘Assembling the brain trust: the multidisciplinary imperative in neuro-oncology’

Author

Aldape, Kenneth, Brindle, Kevin M., Chesler, Louis, Chopra, Rajesh, Gajjar, Amar, Gilbert, Mark R., Gottardo, Nicholas, Gutmann, David H., Hargrave, Darren, Holland, Eric C., Jones, David T. W., Joyce, Johanna A., Kearns, Pamela, Kieran, Mark W., Mellinghoff, Ingo K., Merchant, Melinda, Pfister, Stefan M., Pollard, Steven M., Ramaswamy, Vijay, Rich, Jeremy N., Robinson, Giles W., Rowitch, David H., Sampson, John H., Taylor, Michael D., Workman, Paul, and Gilbertson, Richard J.

Published
2019
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30. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients

Author

Mitchell, Duane A., Batich, Kristen A., Gunn, Michael D., Huang, Min-Nung, Sanchez-Perez, Luis, Nair, Smita K., Congdon, Kendra L., Reap, Elizabeth A., Archer, Gary E., Desjardins, Annick, Friedman, Allan H., Friedman, Henry S., Herndon II, James E., Coan, April, McLendon, Roger E., Reardon, David A., Vredenburgh, James J., Bigner, Darell D., and Sampson, John H.

Subjects
Medical research, Medicine, Experimental, Dendritic cells -- Physiological aspects, Vaccines -- Research, Glioblastoma multiforme -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses (1). As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers (2-4) including glioblastoma (5-7), the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs (8) or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain (9-12), providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy., To evaluate the influence of vaccine site pre-conditioning on DC migration clinically, we conducted a randomized and blinded clinical trial in newly diagnosed glioblastoma (GBM) (Extended Data Fig. 1). A [...]

Published
2015

31. IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.

Author

Swan, Sheridan L., Mehta, Nalini, Ilich, Ekaterina, Shen, Steven H., Wilkinson, Daniel S., Anderson, Alexa R., Segura, Tatiana, Sanchez-Perez, Luis, Sampson, John H., and Bellamkonda, Ravi V.

Subjects
T cells, TREATMENT effectiveness, GLIOBLASTOMA multiforme, CHIMERIC antigen receptors, DENDRITIC cells
Abstract

Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma focus on tumor models that express a single antigen, use immunocompromised animals, and/or pre-treat with lymphodepleting agents. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system that has the potential for tumor eradication. Here, we engineered CAR T cells to express IL7 and/or Flt3L in 50% EGFRvIII-positive and -negative orthotopic tumors pre-conditioned with non-lymphodepleting irradiation. IL7 and IL7 Flt3L CAR T cells increased intratumoral CAR T cell abundance seven days after treatment. IL7 co-expression with Flt3L modestly increased conventional dendritic cells as well as the CD103+XCR1+ population known to have migratory and antigen cross-presenting capabilities. Treatment with IL7 or IL7 Flt3L CAR T cells improved overall survival to 67% and 50%, respectively, compared to 9% survival with conventional or Flt3L CAR T cells. We concluded that CAR T cells modified to express IL7 enhanced CAR T cell abundance and improved overall survival in EGFRvIII heterogeneous tumors preconditioned with non-lymphodepleting irradiation. Potentially IL7 or IL7 Flt3L CAR T cells can provide new opportunities to combine CAR T cells with other immunotherapies for the treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Targeting miR-23a in [CD8.sup.+] cytotoxic T lymphocytes prevents tumor-dependent immunosuppression

Author

Lin, Regina, Chen, Ling, Chen, Gang, Hu, Chunyan, Jiang, Shan, Sevilla, Jose, Wan, Ying, Sampson, John H., Zhu, Bo, and Li, Qi- Jing

Subjects
T cells -- Physiological aspects -- Research, MicroRNA -- Physiological aspects -- Research, Immunosuppression -- Research, Health care industry
Abstract

[CD8.sup.+] cytotoxic T lymphocytes (CTLs) have potent antitumor activity and therefore are leading candidates for use in tumor immunotherapy. The application of CTLs for clinical use has been limited by the susceptibility of ex vivo-expanded CTLs to become dysfunctional in response to immunosuppressive microenvironments. Here, we developed a microRNA-targeting (miRNA-targeting) approach that augments CTL cytotoxicity and preserves immunocompetence. Specifically, we screened for miRNAs that modulate cytotoxicity and identified miR-23a as a strong functional repressor of the transcription factor BLIMP-1, which promotes CTL cytotoxicity and effector cell differentiation. In a cohort of advanced lung cancer patients, miR-23a was upregulated in tumor-infiltrating CTLs, and expression correlated with impaired antitumor potential of patient CTLs. We determined that tumor-derived TGF-β directly suppresses CTL immune function by elevating miR-23a and downregulating BLIMP-1. Functional blocking of miR-23a in human CTLs enhanced granzyme B expression, and in mice with established tumors, immunotherapy with just a small number of tumor-specific CTLs in which miR-23a was inhibited robustly hindered tumor progression. Together, our findings provide a miRNA-based strategy that subverts the immunosuppression of CTLs that is often observed during adoptive cell transfer tumor immunotherapy and identify a TGF-β-mediated tumor immune-evasion pathway., Introduction Owing to their unique abilities for specific tumor antigen recognition and efficient cytolysis, CD8+ cytotoxic T lymphocytes (CTLs) represent the primary leukocyte population used for adoptive cell transfer (ACT) [...]

Published
2014
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37. Just Say 'Charge It!'

Author

Yarema, Connie H. and Sampson, John H.

Abstract

Describes a credit-card-debt activity that allows students to increase their awareness of underlying mathematical concepts relevant to the world of commerce and personal finance through learning geometric and arithmetic sequences. (KHR)

Published
2001

47. Oncolytic polio virotherapy of cancer

Author

Brown, Michael C., Dobrikova, Elena Y., Dobrikov, Mikhail I., Walton, Ross W., Gemberling, Sarah L., Nair, Smita K., Desjardins, Annick, Sampson, John H., Friedman, Henry S., Friedman, Allan H., Tyler, Douglas S., Bigner, Darell D., and Gromeier, Matthias

Published
2014
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