Enhancement of the effectiveness of Lyt-2+ T-cells for adoptive chemoimmunotherapy by short-term exposure of tumor-bearer spleen cells to polyethylene glycol and/or melphalan.
Uncultured tumor-infiltrated spleen cells (TISpC) from mice bearing large (20-22 mm) s.c. MOPC-315 plasmacytomas were previously shown to be ineffective in bringing about the cure of mice bearing a nonpalpable (Day 4) tumor that had been treated with a subcurative dose (10 mg/kg) of cyclophosphamide (i.e., adoptive chemoimmunotherapy, ACIT) (M. B. Mokyr, J. C. D. Hengst, and S. Dray, Cancer Res., 42:974-979, 1982). Here we show that TISpC cultured for 5 days in the presence of inactivated MOPC-315 stimulator cells acquire some effectiveness in curing mice by ACIT, and this effectiveness is greatly enhanced if polyethylene glycol 6000 (PEG) is also added to the culture. The Lyt 2+ T-cells, and not the L3T4+ T-cells, are responsible for the effectiveness of the cultured TISpC in ACIT. In fact, the L3T4+ T-cells are apparently not required even during culture of TISpC for the generation of Lyt 2+ T-cells effective in ACIT. Although the TISpC cultured with MOPC-315 cells and PEG contained approximately twice as many Lyt 2+ cells as did TISpC cultured without PEG, the increase in the activity of the former cells is not due simply to the increase in the percentage of Lyt 2+ cells, but is most likely due to an increase in the percentage and/or activity of Lyt 2+ cells with specificity for MOPC-315-associated antigens. The effectiveness of TISpC cultured with MOPC-315 stimulator cells and PEG in ACIT can be enhanced even further by pretreatment of these cells with the immunomodulating agent melphalan (0.5 nmol/ml) prior to culture initiation. Thus, the above methods of culture render ineffective lymphoid cells effective in ACIT and are suitable for evaluation in protocols for human cancer therapy.
Wise
J A
JA
Department of Microbiology and Immunology, University of Illinois, Chicago 60680.
Mokyr
M B
MB
Dray
S
S
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007116:Immunization, Passive; D008558:Melphalan / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000950:Antigens, Ly; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D008558:Melphalan