Tumor neutralization, immunotherapy, and chemoimmunotherapy of a friend leukemia with cells secondarily sensitized in vitro.

TLDR: Cells generated in a secondary response in vitro were not only cytotoxic in vitro and effective in tumor neutralization, but were also curative in immunotherapy of an early leukemia and in chemoimmunotherapy of a advanced leukemia.

Abstract: The aim of our study was to induce in vitro a secondary response to a C57BL/6 Friend leukemia (FBL-3) by C57BL/6 lymphoid cells, to document their enhanced anti-tumor cytotoxicity in vitro and to study their anti-tumor effect in vivo by tumor neutralization (Winn assay) and tumor therapy of progressive FBL-3 in C57BL/6 mice. Spleen cells (Ci) from mice immunized once in vivo with FBL-3 were cultured for 5 days with either x-irradiated FBL-3 (CiFx), C57BL/6 spleen cells (CiCx), BALB/c spleen cells (CiBx) or without any x-irradiated cells (Ci-cult.) and their activity subsequently was assayed in vitro and in vivo . CiFx cells were markedly more cytotoxic in vitro by the 51 Cr release assay than were CiCx or CiBx and were most effective in tumor neutralization (Winn assay). For adoptive immunotherapy, mice given lethal (10 4 ) FBL-3 i.p. on day 0 received the cultured spleen cells on day 1. Treatment with 5 × 10 6 CiFx cured 14 of 14 mice whereas 19 of 20 mice given 5 × 10 6 CiCx or CiBx died with tumor. For adoptive chemoimmunotherapy of advanced leukemia, mice were given 10 7 FBL-3 i.p. on day 0. On day 5, they received cyclophosphamide (CY) plus cultured spleen cells. Untreated mice died by day 14. CY alone prolonged survival but all mice died within 4 weeks. Treatment with CY plus 5 × 10 6 Ci-cult. or CiBx was no more effective than CY alone—40 of 40 mice died with tumor. However, CY plus 5 × 10 6 CiFx cured 16 of 22 mice. Thus, cells generated in a secondary response in vitro were not only cytotoxic in vitro and effective in tumor neutralization, but were also curative in immunotherapy of an early leukemia and in chemoimmunotherapy of an advanced leukemia.