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6 results on '"Sampson, John"'

2. EGFRvIII-Specific Chimeric Antigen Receptor T Cells Migrate to and Kill Tumor Deposits Infiltrating the Brain Parenchyma in an Invasive Xenograft Model of Glioblastoma

Author

Miao, Hongsheng, primary, Choi, Bryan D., additional, Suryadevara, Carter M., additional, Sanchez-Perez, Luis, additional, Yang, Shicheng, additional, De Leon, Gabriel, additional, Sayour, Elias J., additional, McLendon, Roger, additional, Herndon, James E., additional, Healy, Patrick, additional, Archer, Gary E., additional, Bigner, Darell D., additional, Johnson, Laura A., additional, and Sampson, John H., additional

Published
2014
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3. Myeloablative Temozolomide Enhances CD8+ T-Cell Responses to Vaccine and Is Required for Efficacy against Brain Tumors in Mice

Author

Sanchez-Perez, Luis A., primary, Choi, Bryan D., additional, Archer, Gary E., additional, Cui, Xiuyu, additional, Flores, Catherine, additional, Johnson, Laura A., additional, Schmittling, Robert J., additional, Snyder, David, additional, Herndon, James E., additional, Bigner, Darell D., additional, Mitchell, Duane A., additional, and Sampson, John H., additional

Published
2013
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4. A Pilot Study of IL-2Rα Blockade during Lymphopenia Depletes Regulatory T-cells and Correlates with Enhanced Immunity in Patients with Glioblastoma

Author

Sampson, John H., primary, Schmittling, Robert J., additional, Archer, Gary E., additional, Congdon, Kendra L., additional, Nair, Smita K., additional, Reap, Elizabeth A., additional, Desjardins, Annick, additional, Friedman, Allan H., additional, Friedman, Henry S., additional, Herndon, James E., additional, Coan, April, additional, McLendon, Roger E., additional, Reardon, David A., additional, Vredenburgh, James J., additional, Bigner, Darell D., additional, and Mitchell, Duane A., additional

Published
2012
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6. Myeloablative Temozolomide Enhances CD8+ T-Cell Responses to Vaccine and Is Required for Efficacy against Brain Tumors in Mice.

Author

Sanchez-Perez, Luis A., Choi, Bryan D., Archer, Gary E., Cui, Xiuyu, Flores, Catherine, Johnson, Laura A., Schmittling, Robert J., Snyder, David, Herndon II, James E., Bigner, Darell D., Mitchell, Duane A., and Sampson, John H.

Subjects
BRAIN tumor treatment, IMIDAZOLES, T cells, ALKYLATING agents, BRAIN metastasis, CANCER immunotherapy, CANCER vaccines, CANCER chemotherapy, LABORATORY mice
Abstract

Temozolomide (TMZ) is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be incompatible with immunotherapy. Conversely, it has been proposed that recovery from chemotherapy-induced lymphopenia may actually be exploited to potentiate T-cell responses. Here, we report the first demonstration of TMZ as an immune host-conditioning regimen in an experimental model of brain tumor and examine its impact on antitumor efficacy of a well-characterized peptide vaccine. Our results show that high-dose, myeloablative (MA) TMZ resulted in markedly reduced CD4+, CD8+ T-cell and CD4+Foxp3+ TReg counts. Adoptive transfer of naïve CD8+ T cells and vaccination in this setting led to an approximately 70-fold expansion of antigen-specific CD8+ T cells over controls. Ex vivo analysis of effector functions revealed significantly enhanced levels of pro-inflammatory cytokine secretion from mice receiving MA TMZ when compared to those treated with a lower lymphodepletive, non-myeloablative (NMA) dose. Importantly, MA TMZ, but not NMA TMZ was uniquely associated with an elevation of endogenous IL-2 serum levels, which we also show was required for optimal T-cell expansion. Accordingly, in a murine model of established intracerebral tumor, vaccination-induced immunity in the setting of MA TMZ–but not lymphodepletive, NMA TMZ–led to significantly prolonged survival. Overall, these results may be used to leverage the side-effects of a clinically-approved chemotherapy and should be considered in future study design of immune-based treatments for brain tumors. [ABSTRACT FROM AUTHOR]

Published
2013
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