Current immunotherapy for solid tumors.
Explorative knowledge of cellular and molecular mechanisms of immune function and regulation has provided optimism in developing cancer immunotherapy. However, three decades of experimental and clinical investigations to offer powerful immunotherapeutic strategies against solid tumors, with the possible exception of monoclonal antibody-targeted therapies, have not succeeded in significantly prolonging patient survival. Nonspecific immune approaches, including cytokine-based therapies and allogeneic hematopoietic stem cell transplantation, have so far produced consistent, although limited, results. In this review, we present the developments of cell transfer-based strategies that, in preclinical studies, have demonstrated potential efficacy, but have only established tumor regression in limited numbers of patients. The key to success demands creative combinations of tumor antigens, adjuvance, gene modification and various administration strategies in the development of cell-based therapies together with other cancer-treatment principles, often in a stepwise 'space-rocket-type' approach. Combined efforts of several scientific disciplines, such as tumor biology and immunology, as well as cell and gene research in transplantation, will open new venues. New regulation for clinical trials with advanced therapy medicine products to ensure patient safety will be highlighted.
Barkholt
Lisbeth
L
Division of Clinical Immunology & Transfusion Medicine, Department of Laboratory Medicine, Karolinska University Hospital Huddinge F79, Stockholm, Sweden. lisbeth.barkholt@ki.se
Bregni
Marco
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D019139:Tumor Escape
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D016056:Immunodominant Epitopes