The therapeutic efficacy of murine anti-tumor T cells: freshly isolated T cells are more therapeutic than T cells expanded in vitro

• Published in: Anticancer research Vol. 15; no. 2; p. 441
• Main Authors: Evans, R, Kamdar, S J, Duffy, T M, Krupke, D M, Fuller, J A, Dudley, M E
• Format: Journal Article
• Language: English
• Published: Greece 01.03.1995
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - transplantation; Cell Separation; Cells, Cultured; Combined Modality Therapy; Cyclophosphamide - therapeutic use; Cytotoxicity, Immunologic; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - transplantation; Mice; Mice, Inbred C57BL; Remission Induction; Rhabdomyosarcoma - drug therapy; Rhabdomyosarcoma - immunology; Rhabdomyosarcoma - pathology; Rhabdomyosarcoma - therapy; Soft Tissue Neoplasms - drug therapy; Soft Tissue Neoplasms - immunology; Soft Tissue Neoplasms - pathology; Soft Tissue Neoplasms - therapy; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - transplantation; Thy-1 Antigens - analysis
• ISSN: 0250-7005

Adoptive immunotherapy (AIT) involving transfer of tumor-sensitized T lymphocytes in combination with cyclophosphamide (CY)-injection results in the eradication of the C57BL/6J (B6) rhabdomyosarcoma, 76-9 and is associated with the accumulation of a large number of tumor-infiltrating lymphocytes (TIL). Using immune spleen cells (ISC) from B6 and congenic B6. PL. Thy-1a mice, it was shown that most (> or = 97%) of the TIL were donor-derived. This in situ increase in donor-derived T cells was confirmed by using positively-selected Thy- 1.1+ and Thy- 1.2+ TIL for AIT after isolating them from regressing tumors and expanding them in rIL-2. The extent of CD8+ TIL expansion in vivo correlated with the numbers of TIL adoptively transferred and this in turn determined the degree of anti-tumor effects. It was evident, however, that these in vitro-expanded TIL expressing mRNA for TNF alpha and IFN gamma were qualitatively different and therapeutically less efficacious than the T cells associated with ISC or with freshly-isolated TIL. Unlike freshly isolated TIL that expressed specific cytotoxicity towards the 76-9 targets in vitro, IL-2 expanded TIL killed 76-9 cells and unrelated tumor targets to the same extent. A cytotoxic CD8+ T cell line derived from ISC and selected for activity against the 76-9 tumor cells showed no therapeutic efficacy. The data suggest that, in this tumor model, expansion of CD8+ T cells in vitro selects against anti-tumor efficacy.