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- Title
Transfer of in vitro-expanded naïve T cells after lymphodepletion enhances antitumor immunity through the induction of polyclonal antitumor effector T cells.
- Authors
Tanaka, Tomohiro; Watanabe, Satoshi; Takahashi, Miho; Sato, Ko; Saida, Yu; Baba, Junko; Arita, Masashi; Sato, Miyuki; Ohtsubo, Aya; Shoji, Satoshi; Nozaki, Koichiro; Ichikawa, Kosuke; Kondo, Rie; Aoki, Nobumasa; Ohshima, Yasuyoshi; Sakagami, Takuro; Abe, Tetsuya; Moro, Hiroshi; Koya, Toshiyuki; Tanaka, Junta
- Abstract
The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naïve T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo—expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo—expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo—expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.
- Subjects
T cells; SCURFIN (Protein); PHYSIOLOGY; CYTOPROTECTION; LYMPHOCYTES
- Publication
PLoS ONE, 2017, Vol 12, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0183976