Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

• Published in: Cancer Immunology, Immunotherapy Vol. 57; no. 6; pp. 883 - 895
• Main Authors: Yorty, Jodi L., Tevethia, Satvir S., Schell, Todd D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2008; Springer Nature B.V
• Subjects: Animals; Antigens; Antigens, Polyomavirus Transforming - metabolism; Brain - metabolism; Cancer; Cancer Research; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cytokines - metabolism; Drug dosages; Epitopes - chemistry; Flow Cytometry - methods; Immune System; Immunology; Immunotherapy; Immunotherapy - methods; Kinetics; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Neoplasms - immunology; Neoplasms - metabolism; Oncology; Original Article; Peptides - chemistry; Transgenic animals; Tumors; United States > US; Pennsylvania; SV40 T antigen; T cells; CD8; Immunotherapy; Transgenic mice
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-007-0424-y

We previously established a model to study CD8 + T cell (T CD8 )-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant T CD8 -recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from naïve C57BL/6 (B6) mice prolongs SV11 survival following T CD8 priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific T CD8 accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or naïve donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific T CD8 accumulated to high levels in the brain of SV11 mice, peaking at 5–7 days, while epitope IV-specific T CD8 derived from naïve donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific T CD8 accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor T CD8 play a predominant role in control of tumor growth.