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

Abstract

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.

• Authors: R Evans, S J Kamdar, T M Duffy, D M Krupke, J A Fuller, M E Dudley
• Journal: Anticancer research (Anticancer Res) 1995 Mar-Apr Vol. 15 Issue 2 Pg. 441-7 ISSN: 0250-7005 [Print] Greece
• PMID: 7763019 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Thy-1 Antigens
• Cyclophosphamide

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, transplantation)
• Cell Separation
• Cells, Cultured
• Combined Modality Therapy
• Cyclophosphamide (therapeutic use)
• Cytotoxicity, Immunologic
• Immunotherapy, Adoptive
• Lymphocytes, Tumor-Infiltrating (immunology, transplantation)
• Mice
• Mice, Inbred C57BL
• Remission Induction
• Rhabdomyosarcoma (drug therapy, immunology, pathology, therapy)
• Soft Tissue Neoplasms (drug therapy, immunology, pathology, therapy)
• T-Lymphocyte Subsets (immunology, transplantation)
• Thy-1 Antigens (analysis)