Classification of current anticancer immunotherapies

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches

Anti-tumor Immunity of Gene Vaccine with Nucleofection Technology

OBJECTIVE To observe enhancement of anti-tumor immunity by gene vaccine using nucleofection technology.METHODS The technique of nucleofection was used to transfereffectively plasmid DNA into immature dendritic cells (iDCs); we studied immune responses regulated by DNA vaccine using real-time quantitative polymerase chain reaction (PCR) and Western-blotting to optimize the follow-up lymphocyte activation. The anti-tumor capacity of lymphocytes primed by DCs was analyzed using lactate dehydrogenase with a non-radioactive cytotoxicity assay.RESULTS Human monocyte-derived dendritic cells (hMoDCs) were induced by interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro from human monocytes for 5 or 6 days. DNA vaccine was transfected to iDCs with high transfection (35.73%) using nucleofection. Compared with the iDC group, the expression of Th1 cell cytokine IL-12, IL-18 and Th2 cell cytokine IL-4 increased after stimulation. CD86 and CD83 were upregulated compared with non-nucleofected groups 48 hours after nucleofection with DC-pVAX-PRA. The result of the cytotoxicity assay showed that DCs-pVAX-PRA primed non-adherent peripheral blood mononuclear cells (PBMCs) exhibit their highest cytotoxicity against target cells.CONCLUSION The results show that DNA vaccine was transfected to iDC with high transfection efficiency using nucleofection, priming autologous lymphocytes for anti-tumor immunity by upregulated expression of co-stimulatory molecules, adhesion molecules and cytokines. These results provided a basis to explore the molecular mechanism of DNA vaccine in vivo

The Human Vaccines Project: A roadmap for cancer vaccine development.

Cancer vaccine development has been vigorously pursued for 40 years. Immunity to tumor antigens can be elicited by most vaccines tested, but their clinical efficacy remains modest. We argue that a concerted international effort is necessary to understand the human antitumor immune response and achieve clinically effective cancer vaccines