Efficient tumor antigen loading of dendritic antigen presenting cells by transimmunization.
Extracorporeal photochemotherapy (ECP), or photopheresis, was originally introduced for the management of patients with cutaneous T cell lymphoma (CTCL). Today, ECP remains the only FDA approved tumor-targeting selective immunotherapy for the treatment of any cancer. The key cellular events permitting ECP-induced anti-tumor immunity against CTCL are the induction of apoptotis in the malignant T cells, and the induction of monocyte-to-dendritic cell (DC) differentiation. In standard ECP, leukocytes extracorporeally exposed to psoralen and ultraviolet A light (UVA) are circulated back to the patient. However, recent findings suggest that co-incubation of these cells prior to re-infusion allows for more efficient phagocytosis and processing of the apoptotic malignant T cells by the newly formed DCs. Moreover, such a co-incubation step permits the direct external manipulation of this system and the design of strategies to augment the production of tumor-loaded DCs. These considerations have led to the development of Transimmunization, so named because it causes transfer of tumor antigens to newly formed dendritic cells capable of initiating immunization against the tumor cells, as the replacement technology for ECP. We will review the scientific understanding of ECP and explain how this can lead a more efficient, potentially broadly applicable, immunotherapy for cancer.
Girardi
Michael
M
Department of Dermatology, Yale Univesity School of Medicine, New Haven CT 06520, USA. michael.girardi@yale.edu
Berger
Carole
C
Hanlon
Douglas
D
Edelson
Richard L
RL
D000938:Antigen-Presenting Cells / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism* / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007114:Immunization / Q000379:methods*; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D017893:Photopheresis / Q000379:methods
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines