Immune adjuvants for chemotherapy or radiotherapy in the 9L rat brain tumor model.

The therapeutic efficacy and toxicity of three biological response modifiers, Corynebacterium parvum (Cp), Chinese blister beetle extract (CBBE), recombinant human IL-1 alpha (rhIL-1 alpha), used alone or in combination with chemotherapy or radiotherapy, were investigated in the intracerebral (ic) rat 9L brain tumor model. Used alone, Cp (2 mg/rat, ip plus 70 micrograms/rat, ic), CBBE (5 microliters of an ethanol extract, ic), or IL-1 alpha (1 microgram/rat, ic or 1 microgram/rat x 3, q 3 d, ic), had no effect on animal survival compared to the untreated or saline treated controls. When combined with chemotherapy or radiotherapy, the three immunotherapeutic agents did not show any additive effects on survival compared to that observed with systemic BCNU (12 mg/kg), local ic bleomycin (0.25 unit), or local radiotherapy (16 Gy). While ic IL-1 alpha did not produce evident toxicity, there was fatal toxicity caused by ic Cp or CBBE treatment in a few animals. The combination of Cp and bleomycin produced severe neurotoxicity, resulting in the early death of animals. This study demonstrates a lack of efficacy of the nonspecific immune adjuvants IL-1 alpha, Cp or CBBE, used either alone or combined with cytotoxic chemotherapy or radiotherapy, in this rat brain tumor model.