2 TUMOR-MODELS OF CURATIVE ADOPTIVE CHEMOIMMUNOTHERAPY USING TUMOR-INFILTRATED SPLEEN-CELLS WITH POTENT ANTITUMOR CYTOTOXICITY STIMULATED BY ANTIGEN-SHARING TUMORS

Previously we have established curative protocols for adoptive chemoim munotherapy (ACIT) of mice bearing different plasmacytomas that are kn own to bear cross-reacting antigens: (a) the cure of mice bearing an e arly-stage, nonpalpable MOPC-315 tumor by a very low dose of cyclophos phamide (10 mg/kg) and cultured MOPC-315-tumor-infiltrated (TI) spleen cells (25 x 10(6)) and (b) the cure of mice bearing a late-stage, rel atively drug-resistant, highly metastatic RPC-5 tumor with cyclophosph amide (100 mg/kg) and cultured RPC-5 TI spleen cells (25 x 10(6) - 50 x 10(6)). In both models, the spleen cells were obtained from mice bea ring a late-stage tumor and were cultured for 5 days in the presence o f polyethyleneglycol 6000 and autochthonous tumor cells as a source of tumor antigen. Here we show that RPC-5 tumor cells could substitute f or MOPC-315 tumor cells in the 5-day culture of MOPC-315 TI spleen cel ls so that they became curative in ACIT for mice bearing an early-stag e MOPC-315 tumor. Similarly, MOPC-315 tumor cells could substitute for RPC-5 tumor cells in the 5-day culture of RPC-5 TI spleen cells so th at they became curative in ACIT of mice bearing a late-stage RPC-5 tum or. In addition, RPC-5 TI spleen cells cultured with either MOPC-315 o r RPC-5 tumor cells were effective in curing all mice bearing an early -stage MOPC-315 tumor by ACIT. However, MOPC-315 TI spleen cells wheth er cultured with MOPC-315 or RPC-5 tumor cells, were much less effecti ve than cultured RPC-5 TI spleen cells in curing mice bearing a late-s tage RPC-5 tumor by ACIT (although die survival of these mice was exte nded significantly). Interestingly, whereas RPC-5 TI spleen cells cult ured with either MOPC-315 or RPC-5 tumor cells were as effective as MO PC-315 TI spleen cells cultured under the same conditions in lysing MO PC-315 tumor cells in vitro, MOPC-315 TI spleen cells that had been cu ltured with either MOPC-315 or RPC-5 tumor cells exerted a much weaker in vitro cytotoxic T lymphocyte activity against RPC-5 tumor cells th an did RPC-5 TI spleen cells that had been cultured under the same con ditions.