SUPPRESSION OF THE INVITRO SECONDARY RESPONSE TO SYNGENEIC TUMOR AND OF INVIVO TUMOR-THERAPY WITH IMMUNE CELLS BY CULTURE-INDUCED SUPPRESSOR CELLS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 123  (2) , 515-522
Abstract
Mice with advanced disseminated syngeneic tumor can be successfully treated with a combination of chemotherapy and adoptively transferred syngeneic immune cells. It was previously demonstrated that in vivo primed cells secondarily sensitized in vitro became more effective in tumor therapy, whereas primed cells cultured for 5 days without tumor stimulation became less effective than an equal number of uncultured fresh primed cells. Stimulated and unstimulated cultures of tumor-primed cells were examined for the presence of culture-induced suppressor cells, and it was determined whether in vivo tumor therapy with immune cells could be inhibited by concurrent inoculation of immune effector cells and cultured normal spleen cells, which contain culture-induced suppressor cells but are devoid of additional effector cells. The in vitro primary allogeneic response was suppressed by cultured normal spleen cells, or tumor-primed spleen cells previously cultured for 5 days with or without tumor stimulation. In vitro secondary sensitization to syngeneic tumor was suppressed by normal or tumor-primed cells that had previously been cultured for 5 days without stimulation. The majority of this suppression was mediated by T [thymus-derived] cells in the cultured populations. The efficacy of fresh tumor-primed cells, and primed cells secondarily sensitized in vitro, in adoptive chemoimmunotherapy of advanced tumor was diminished by concurrent inoculation of cultured normal cells. The cells mediating suppression of in vivo therapy required previous in vitro culture for induction, and were radiation sensitive.