Cure of mice bearing a late-stage, highly metastatic, drug-resistant tumor by adoptive chemoimmunotherapy.

We show here that in contrast to BALB/c mice bearing a late-stage, large MOPC-315 plasmacytoma, BALB/c mice bearing a late-stage, large RPC-5 plasmacytoma were not cured by cyclophosphamide therapy (15, 50, 100 or 200 mg/kg). However, most BALB/c mice bearing a late-stage RPC-5 tumor were cured by cyclophosphamide therapy (100 mg/kg) in conjunction with adoptive immunotherapy using tumor-infiltrated spleen cells (TISpC) that had been cultured with inactivated RPC-5 tumor cells plus polyethylene glycol 6000, even though this protocol was not effective for the therapy of mice bearing a barely palpable, early-stage RPC-5 tumor. Only a few of the mice that were cured of a late-stage RPC-5 tumor following adoptive chemoimmunotherapy (ACIT) were resistant to a subsequent challenge with RPC-5 tumor cells. However, the challenged mice that had developed progressively growing tumors could then be cured by cyclophosphamide alone when the tumor became large, even though this treatment was not curative for mice bearing a tumor of similar size but not previously treated by ACIT. Thus, the cure by ACIT of BALB/c mice bearing a lethal, late-stage RPC-5 tumor with extensive metastases provides a novel experimental tumor model for investigating the mechanisms by which a chemotherapeutic drug and adoptive cellular immunotherapy can cooperate in causing the complete regression of a large tumor load.