THE THERAPEUTIC EFFICACY OF MURINE ANTITUMOR T-CELLS - FRESHLY ISOLATED T-CELLS ARE MORE THERAPEUTIC THAN T-CELLS EXPANDED IN-VITRO

Adoptive immunotherapy (AIT) involving transfer of tumor-sensitized T lymphocytes in combination with cyclophosphamide (CY)-injection result s in the eradication of the C57BL/6J (B6) rhabdomyosarcoma, 76-9 and i s associated with the accumulation of a large number of tumor-infiltra ting lymphocytes (TIL). Using immune spleen cells (ISC) from B6 and co ngenic B6. PL. Thy-1(alpha) mice, it was shown that most (greater than or equal to 97%) of the TIL were donor-derived. This in situ increase in donor-derived T cells was confirmed by using positively-selected t hy-1.1(+) and Thy- 1.2(+) TIL for AIT after isolating them from regres sing tumors and expanding them in rIL-2. The extent of CD8(+) TIL expa nsion in vivo correlated with the numbers of TIL adoptively transferre d and this in turn determined the degree of anti-tumor effects. It was evident, however, that these in vitro-expanded TIL expressing mRNA fo r TNF alpha and IFN gamma were qualitatively different and therapeutic ally less efficacious than the T cells associated with ISC or with fre shly-isolated TIL. Unlike freshly isolated TIL that expressed specific cytotoxicity towards the 76-9 targets in vitro, IL-2 expanded TIL kil led 76-9 cells and unrelated tumor targets to the same extent. A cytot oxic CD8(+) T cell lines derived from ISC and selected for activity ag ainst the 76-9 tumor cells showed no therapeutic efficacy. The data su ggest that, in this tumor model, expansion of CD8(+) T cells in vitro selects against anti-tumor efficacy.