Claude Roth

Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2.

Summary Electrochemotherapy is an antitumor treatment that combines a cytotoxic drug with the local administration of electric pulses delivered at the tumor site. We previously found that in mice the cure rate of subcutaneous transplanted tumors treated by electrochemotherapy is increased by repeated systemic interleukin-2 (IL-2) injections. Moreover, histoincompatible cells engineered to secrete IL-2 allow the rejection of syngeneic tumor cells when both cells are inoculated together. In this study of preestablished tumors in mice we show that after electrochemotherapy, delayed peritumoral injections of histoincompatible IL-2-producing cells result in the cure of almost all the tumors. Moreover, this combined local treatment leads to cures of untreated, contra-laterally transplanted tumors. This systemic antitumor immunity also resulted in complete protection of the cured mice against further inocula of the tumor cells. These results, which were obtained using allogeneic as well as xenogeneic IL-2-secreting cells, suggest that electrochemotherapy combined with such cellular immunotherapy might be a useful approach for the treatment of metastasizing cancers.

IMMUNE RESPONSE AGAINST TUMORS

Publisher Summary The chapter reviews a number of aspects related both to the antigenicity and the immunogenicity of tumors. The chapter could not cover the entire field and have selected what felt as the most relevant trends in current research. The chapter reviews a number of aspects dealing with immune responses directed against and stimulated by tumor cells. In particular, there are many other ways to try and overcome the poor immunogenicity of tumor cells, especially with respect to the modifications of antigen presenting cells and to the use of various gene therapy protocols. The notion of tumor specific antigens, which initially involved integral cell-surface proteins recognized by antibodies, has been extended to T-cell epitopes presented by major histocompatibility complex (MHC) molecules and recognized by specific T cells. The field of tumor immunology has then largely shifted toward the analysis and manipulation of T-cell responses. A new conceptual framework has opened up new experimental approaches. Results now obtained in animal models have become so spectacular that expectations have been raised concerning the prospects for the immunotherapy of human cancers. An understandable trait of tumor immunology is that every finding is almost immediately framed within a therapeutic perspective. This may explain the confusion, commonly encountered in the field, between an antigen and an immunogen, because any antigen is immediately used as an immunogen for trying to control tumor growth.