Eradication of a disseminated syngeneic mouse lymphoma by systemic adoptive transfer of immune lymphocytes and its dependence upon a host component(s)

Abstract

We have studied the in vivo effects of carrageenan and trypan blue on the adoptive immunotherapy of an established local and disseminated syngeneic mouse FBL-3 lymphoma. Mice receiving 500 rads total-body irradiation before injection of FBL-3 tumor into the footpad were treated 4 to 5 days later when a palpable local tumor and disseminated metastases were present. Injection of in vivo immune lymphocytes i.v. caused complete regression of footpad tumor and cured 96% of all mice (greater than 60 days mean survival; p less than 0.0005). Carrageenan or trypan blue treatment of the tumor-bearing host abrogated the therapeutic effect of adoptively transferred cells. Cure rates were significantly reduced to 27% (p less than 0.004) and 0% (p less than 0.0001) and mean survival times to 40.2 days (p less than 0.0005) and 15.2 (p less than 0.005) days for mice treated with carrageenan and trypan blue, respectively, in addition to immune cells. In vivo treatment of the immune spleen cell donors with carrageenan or trypan blue had no significant effect on the ability of those splenocytes to mediate cure when adoptively transferred into tumor-bearing hosts, indicating that the inhibitory activity of these agents cannot be attributed to direct toxicity to immune lymphoid cells. These results demonstrate that a recipient component(s), possibly macrophages, sensitive to carrageenan and to trypan blue but relatively resistant to radiation (500 rads), plays a vital role in the cure of tumor-bearing mice that receive the adoptive transfer of immune splenocytes.