Active specific immunotherapy with extracted tumor-specific transplantation antigen, cyclophosphamide, and adoptive transfer of tumor-specific cytotoxic T-cell clones.
An L3T4-, Lyt2+ tumor-specific, cloned T-lymphocyte cell line (RTT-2) was isolated from a spleen cell population harvested from C3H/HeJ mice, following in vivo immunization against a syngeneic MCA-induced fibrosarcoma (MCA-F) and in vitro restimulation with 1-butanol-extracted, isoelectrophoretically purified MCA-F tumor-specific transplantation antigen (TSTA). RTT-2 required exposure to homotypic-extracted MCA-F TSTA in combination with low-dose IL-2 to maintain its specific cytotoxic activity in vitro. In vivo local adoptive transfer of RTT-2 caused specific neutralization of homotypic MCA-F, but not heterotypic MCA-D, tumor cells. Systemic in vivo transfer of RTT-2 alone augmented host resistance. In combination with a triple regimen of weekly doses of purified TSTA (1 microgram SC) and a single ip injection of CY (20 mg/kg), adoptive transfer of RTT-2 cells (1 X 10(7)) retarded the neoplastic outgrowth in and prolonged the survival of primary hosts bearing 3-, 7-, and 14-day established MCA-F tumors. In a spontaneous pulmonary metastasis model following amputation of a tumor-bearing limb, the triple regimen of TSTA/CY/RTT-2 markedly reduced the number of lung colonies. Thus RTT-2, which displays specific tumoricidal activity in vitro and in vivo, may afford a suitable tool to dissect T-cell receptors recognizing tumor markers on 1-butanol-extracted, MCA-F TSTA.
Naito
K
K
Department of Surgery, University of Texas Medical School, Houston 77030.
Pellis
N R
NR
Kahan
B D
BD
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002455:Cell Division; D003520:Cyclophosphamide / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D007116:Immunization, Passive; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D012513:Sarcoma, Experimental / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D000951:Antigens, Neoplasm; D007376:Interleukin-2; D003520:Cyclophosphamide