Journal
ONCOIMMUNOLOGY
Volume 4, Issue 5, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2014.1002723
Keywords
adoptive T-cell transfer; CD4+THELPER1 cells; cell cycle arrest; immunotherapy; polyfunctional T cells
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB685]
- German Federal Ministry of Science and Education (BMBF, iVAC-ALL)
- Fortune-program (University of Tubingen) [1892-0-0, 1977-0-1]
- European Social Fund in Baden-Wurttemberg
- Institutional Strategy of the University of Tubingen (Deutsche Forschungsgemeinschaft) [ZUK 63]
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Tumor-associated antigens such as NY-ESO-1 are expressed in a variety of solid tumors but absent in mature healthy tissues with the exception of germline cells. The immune system anti-cancer attack is mediated by cell lysis or induction of growth arrest through paralysis of tumor cells, the latter of which can be achieved by tumor-specific CD4(+), IFN-producing T-Helper type 1 (T(H)1) cells. Translation of these immune-mediated mechanisms into clinical application has been limited by availability of immune effectors, as well as the need for complex in vitro protocols and regulatory hurdles. Here, we report a procedure to generate cancer-testis antigen NY-ESO-1-targeting CD4(+) T(H)1 cells in vitro for cancer immunotherapy in the clinic. After in vitro sensitization by stimulating T cells with protein-spanning, overlapping peptide pools of NY-ESO-1 in combination with IL-7 and low dose IL-2, antigen-specific T cells were isolated using IFN capture technique and subsequently expanded with IL-2, IL-7 and IL-15. Large numbers of NY-ESO-1-specific CD4(+) T cells with a T(H)1 cytokine profile and lower numbers of cytokine-secreting CD8(+) T cells could be generated from healthy donors with a high specificity and expansion potential. Manufactured CD4(+) T cells showed strong specific T(H)1-responses with IFN+, TNF+, IL-2(+) and induced cell cycle arrest and apoptosis in tumor cells. The protocol is GMP-grade and approved by the regulatory authorities. The tumor-antigen specific CD4(+) T(H)1 lymphocytes can be adoptively transferred as a T-cell therapy to boost anticancer immunity and this novel cancer treatment approach is applicable to both T cells from healthy allogeneic donors as well as to autologous T cells derived from cancer patients.
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