Evaluation of various cytostatic drugs as local immunotherapeutic agents

The cytostatic drugs methotrexate, 5-fluorouracil, adriamycin, vincristin, cisplatinum, VP-16 and the newly synthesized, stabile cyclophosphamide-derivative Z-7557, were screened for possible immunopotentiating effects in local chemotherapy. With an in vivo contact sensitivity model in guinea pigs, low dosages of the drugs were introduced into antigenically stimulated lymph nodes by intradermal injections following sensitization. Marked till strong potentiation of T-cell function, as measured by the development of contact hypersensitivity, was observed with all drugs tested, except for methotrexate and 5-fluorouracil. With a similar local chemotherapeutic protocol in the guinea pig line 10 hepatocellular carcinoma-model, these latter drugs have been reported earlier to be exceptional in failing to induce tumor regression and tumor immunity. Our present results suggest that local chemotherapy of malignancies not only may reduce local tumor load, but also may affect distant metastases by facilitating the development of tumor-specific immunity.