Chemo-immunotherapy and chemo-adoptive immunotherapy of cancer

Abstract

The chemo-immunotherapy (CIT) and chemo-adoptive immunotherapy (CAIT) regimens tested in the past decade are summarized. From them we have learned a great deal about the interactions between various chemotherapeutic agents, immune modulating agents and effector cells. The most commonly reported result in multi-modality experiments with CAIT has been a synergistic enhancement in antitumor activity. Clinical trials usually demonstrated improvement in patient quality of life, an extension of survival time, and occasional complete regression of tumor. In many animal models, this enhancement often meant the complete regression and apparent cure of tumor in the animal. One mechanism by which this synergistic enhancement takes place appears to be a suppression of tumor-associated suppressor T cell activity by the chemotherapeutic agents, thereby inducing enhanced cytolytic activity against tumor by the adoptively transferred, activated effector cells. In CAIT the most commonly used drug has been cyclophosphamide. In CIT a wide variety of chemotherapy agents have been used but none of the clinical trials made use of cyclophosphamide. Thus, direct comparisons are not possible. Suggestive of the intricate regulatory processes involved, many CIT studies indicate a synergy only when specific doses of chemotherapy and immunotherapy agents are given, and in a specific sequence. CIT has become less toxic, is being handled on a cost-effective outpatient basis, while maintaining similar objective response rates to earlier inpatient treatments. In the future, CAIT and CIT will probably have an increasing role in the management of patients with specific cancers.