Rapid generation of NY-ESO-1-specific CD4 + T HELPER 1 cells for adoptive T-cell therapy

• Published in: Oncoimmunology Vol. 4; no. 5; p. e1002723
• Main Authors: Kayser, Simone, Boβ, Cristina, Feucht, Judith, Witte, Kai-Erik, Scheu, Alexander, Bülow, Hans-Jörg, Joachim, Stefanie, Stevanović, Stefan, Schumm, Michael, Rittig, Susanne M, Lang, Peter, Röcken, Martin, Handgretinger, Rupert, Feuchtinger, Tobias
• Format: Journal Article
• Language: English
• Published: United States 04.05.2015
• Subjects: polyfunctional T cells; DC, dendritic cell; CD4+ THELPER1 cells; Treg, regulatory T cell; TH1, THelper1; ACT, adoptive T cell transfer; cell cycle arrest; NK, natural killer; CTL, cytotoxic T lymphocyte; adoptive T-cell transfer; immunotherapy; GMP, good manufacturing practice; TIL, tumor-infiltrating lymphocyte
• DOI: 10.1080/2162402X.2014.1002723
• ISSN: 2162-4011; 2162-402X

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 , IFNγ-producing T type 1 (T 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 protocols and regulatory hurdles. Here, we report a procedure to generate cancer-testis antigen NY-ESO-1-targeting CD4 T 1 cells 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 IFNγ 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 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 1-responses with IFNγ , TNFα , 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 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.