Chemotherapy followed by syngeneic dendritic cell injection in the mouse: findings and implications for human treatment.
A growing number of studies have described an apparent synergy between systemic chemotherapy administration and the intratumoral injection of dendritic cells (DCs) in the successful treatment of murine tumors. A review of several of these studies is undertaken here and possible combinations of DC therapy and conventional cancer therapies are discussed with the goal of contemplating the exploitation of current findings and theory toward the treatment of human patients with cancer. The methods and results of several murine studies are described in detail and additional reference is made to other relevant murine studies. Hypothetical routes of synergy between DC therapy, chemotherapy, and ablative therapies are explored, and the potentially significant role played by the regulatory immune system is discussed. Given the results of preclinical studies and the current understanding of cancer immunity, it is possible to consider a human treatment that calls for focal ablation of cancer followed by intratumoral DC injection, in the setting of chemotherapy-based regulatory T-cell depletion.
Cavanagh
William A
WA
Haakon Ragde Foundation for Advanced Cancer Studies, Seattle, Washington 98109, USA. Bill@HaakonRagdeFoundation.org
Tjoa
Benjamin A
BA
Ragde
Haakon
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017690:Cell Transplantation / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D008495:Medical Oncology / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism
D000970:Antineoplastic Agents