Dendritic cell-based vaccines in cancer: Clinical experience to date
Therapeutic vaccines that can activate the immune system to destroy malignancies hold the promise of a low-toxicity, precisely targeted anticancer treatment modality. Because dendritic cells (DCs) are central to the activation of antigen-specific immune responses, DCs loaded with tumor antigens are of considerable interest as therapeutic vaccines. Preclinical studies have demonstrated the potency of DC-based immunizations in promoting tumor rejection. Continued preclinical and clinical studies are assessing a number of important parameters regarding the formulation and administration regimen of DC-based vaccines and have provided support for phase I and II studies. Thus far, DC-mediated immunizations have been well tolerated, with few toxicities reported. Tumor regression has been reported in up to 30% of patients, particularly with immunologically sensitive tumors such as melanoma. Biologic activity, measured as activation of antigen-specific T cells, is reported in up to 100% of patients immunized against potent recall antigens, such as tetanus toxoid, and up to 30% of those immunized against tumor antigens. Current clinical trials are increasingly testing DC-based vaccines in patients with minimal residual disease, such as following attempted curative surgery or following high-dose chemotherapy and stem-cell support where clinical benefit is likely to be the greatest. Newer strategies are focusing on further modifications to DCs to increase their immunostimulatory potency. These include newer methods of antigen loading, better techniques for DC maturation, strategies to enhance polarization of DCs to ensure the induction of T helper cell type 1 immune responses, and the administration of adjunctive cytokines to augment the immune response following immunization.
Morse, MA; Mosca, PJ; Clay, TM; Lyerly, HK
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