REQUIREMENTS FOR SUCCESSFUL IMMUNOTHERAPY AND CHEMO-IMMUNOTHERAPY OF A MURINE MODEL OF OVARIAN-CANCER

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (3) , 980-983
Abstract
A comprehensive study of nonspecific immunotherapy was conducted in an established murine model of ovarian cancer to determine the relative effectiveness of commonly used bacterial immunostimulants, the importance of the route and schedule of administration of these agents and their effects in combination with chemotherapy. Implants of 105 or 106 ovarian tumor cells i.p. kill all syngeneic C3HeB/FeJ mice within 25 days. Corynebacterium parvum [Propionibacterium acnes] (700 .mu.g/mouse i.p. 24 h after a 105 tumor cell inoculum) cures 75% of the mice; neither i.v. nor s.c. administration improves survival rates. After the same tumor challenge, BCG was minimally effective at extremely high doses only; the methanol extraction residue of BCG was ineffective. Two days after an implant of 106 tumor cells, neither cyclophosphamide, cis-diamminedichloroplatinum(II) (cisplatin) nor C. parvum increased survival. Combination of C. parvum with cyclophosphamide or cisplatin resulted in a synergism shown by the 40 and 60% cure rates, respectively. Combination of C. parvum with an active agent, doxorubicin, resulted in toxicity even in untumored animals. Therapeutic efficacy of immunotherapy apparently depends critically on the choice of an appropriate agent and route of administration and, to a lesser extent, on the dose and schedule used. The observation provides a rationale for carefully conducted Phase I and Phase II studies of treatment with bacterial immunostimulants, alone or in combination with chemotherapy, in human ovarian cancer.