4.6 Article

TCR gene therapy of spontaneous prostate carcinoma requires in vivo T cell activation

Journal

JOURNAL OF IMMUNOLOGY
Volume 181, Issue 4, Pages 2563-2571

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.4.2563

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Funding

  1. NCI NIH HHS [R37 CA025000, R01 CA025000, CA-25000, R01 CA025000-30] Funding Source: Medline

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Analogous to the clinical use of recombinant high-affinity Abs, transfer of TCR genes may be used to create a T cell compartment specific for self-Ags to which the endogenous T cell repertoire is immune tolerant. In this study, we show in a spontaneous prostate carcinoma model that the combination of vaccination with adoptive transfer of small numbers of T cells that are genetically modified with a tumor-specific TCR results in a marked suppression of tumor development, even though both treatments are by themselves without effect. These results demonstrate the value of TCR gene transfer to target otherwise nonimmunogenic tumor-associated self-Ags provided that adoptive transfer occurs under conditions that allow in vivo expansion of the TCR-modified T cells.

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