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Generation of CTL Lines with Specificity Against Multiple Tumor Antigens

技术优势

- Multi-TAA CTLs are polyclonal in antigen recognition, polyfunctional for cytokine production, and cytolytic against tumor cells.- Multi-TAA CTLs can be generated from both healthy donors and cancer patients, irrespective of HLA genotype, significantly broaden its potential clinical application.- Besides lymphoma, with different combinations of TTAs, this strategy may be used to target various types of cancers.

详细技术说明

Publications:Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphoma. Gerdemann U, Katari U, Christin AS, Cruz CR, Tripic T, Rousseau A, Gottschalk SM, Savoldo B, Vera JF, Heslop HE, Brenner MK, Bollard CM, Rooney CM, Leen AM. Mol Ther. 2011 Dec;19(12):2258-68.

*Abstract

Nonviral tumor-associated antigens (TAAs) are challenging targets for T-cell therapy. As self-antigens, TAAs are relatively weak stimulators of T-cell immunity. Hence, efforts to extend T-cell therapy to nonviral tumors has been limited by an inability to consistently activate and expand endogenous tumor-reactive T cells directed against the TAAs.Our researchers developed a novel strategy to generate cytotoxic T lymphocyte (CTL) lines with specificity for multiple TAAs frequency expressed by tumor cells. Using this strategy, the researchers generated CTLs that recognize a wide spectrum of nonviral TAAs expressed in lymphoma, including Survivin, MAGE-A4, Synovial sarcoma X (SSX2), preferentially expressed antigen in melanoma (PRAME) and NY-ESO-1. Multi-TAA CTLs were successfully generated from healthy donors and lymphoma patients, irrespective of HLA type. The resultant multi-TAA CTLs were able to produce multiple proinflammatory cytokines and demonstrated cytolytic activity against autologous tumor cells and their clinical impact is currently being tested in an NIH-funded Phase I clinical trial.

国家/地区

美国