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IL12 polarization of mouse and human T‐cells: implications for adoptive immunotherapy
Author(s) -
Johnson Laura Alexandra,
Kaiser Andrew,
Paulos Chrystal M,
Powell Daniel J,
Heemskerk Bianca,
Restifo Nicholas P,
Rosenberg Steven A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1077.19
Subject(s) - interleukin 12 , adoptive cell transfer , t cell receptor , immunology , foxp3 , antigen , interleukin 21 , cancer research , biology , t cell , in vitro , microbiology and biotechnology , chemistry , cytotoxic t cell , immune system , cd8 , biochemistry
Adoptive immunotherapy with TCR transduced autologous PBL can mediate objective clinical responses in patients with advanced metastatic melanoma. Different factors affecting adoptively transferred cells include avidity and affinity of the TCR, TCR expression, differentiation state, and immunological phenotype of the transferred cells. In vitro, naïve murine splenocytes can be polarized into Type 1, 2 or 3 (Treg) cells by TCR activation in the presence of specific cytokines. Here we show both TCR‐specific murine and human T‐cells can be polarized into a Type 1 phenotype by TCR stimulation in presence of IL12, using whole PBL or naïve T‐cells. In both models, IL12 polarized T‐cells produced the most IFNg in response to tumor antigen stimulation, and had the highest lytic capabilities against cognate antigen‐bearing tumor targets in vitro. Unexpectedly, IL12 programmed human T‐cells demonstrated a reduction in FoxP3+CD4+ cells, suggesting reduced Tregs, while maintaining similar expansion. We found that IL12 polarization of TCR‐specific T‐cells from both mouse and human donors resulted in similar in vitro anti‐tumor phenotypes. These results, combined with our finding that IL12 polarized cells demonstrated superior tumor regression on established tumors in an animal model, suggest the potential to utilize IL12 polarization of TCR transduced human PBL in the clinic to treat patients with cancer.