In the early 1970s supervised clinical trials were initiated at The University of Texas M.D. Anderson Hospital in Houston, TX, for the combination of viral oncolysate-based vaccines and contemporary chemotherapy for the treatment of patients with metastatic melanoma and sarcomas. This therapeutic approach was then generally considered to be inappropriate based on a widely held belief that the efficacy of cancer vaccines would be negated by the immunosuppressive effects of the chemotherapy. Not NCI grants, but institutional funds supported these clinical trials. These early clinical trials included in vitro tests for anti-tumor cell antibodies and cytotoxic lymphocytes both in autologous and allogeneic settings and showed that these faculties remained active even after chemotherapy. The contemporary reports of unexpectedly favorable clinical results are recited in this article. Despite these most promising results, support from federal granting agencies (the NIH/NCI) was repeatedly denied; these denials were based on the prevailing dogma that the two treatment modalities are expected to be antagonistic and not synergistic or not even additive. However, thirty years later, now in the new era of molecular medicine, a rapidly increasing number of peer-reviewed publications appear and offer convincing evidence that strongly substantiate the therapeutic value of combined cancer chemoimmunotherapy. The important provision is that the sequencing and dosing of the two major treatment modalities, the vaccination and the chemotherapy, are to be pre-tested and then the methodology is to be adhered to in the new clinical trials. New sophisticated experiments carried out in vitro and in vivo and subsequent clinical trials attest to the potential value of this combinatory approach and explain the underlying molecular mechanisms. This pragmatic review recapitulates the empirically administered earliest clinical trials, and lists and interprets, in view of their molecular immunomodulatory effects, the exemplary new clinical trials.

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