Optimizing dendritic cell-based immunotherapy for cancer

Abstract

Dendritic cells (DCs) are the most powerful professional antigen-presenting cells and are unique in their capability to initiate, maintain and regulate the intensity of primary immune responses, including specific antitumor responses. Development of practical procedures to prepare sufficient numbers of functional human DCs in culture from the peripheral blood precursors, paved the way for clinical trials to evaluate various DC-based strategies in patients with malignant diseases. However, no definite conclusions regarding the clinical and even immunological efficacy of DC vaccination can be stated, despite the fact that 12 years have passed since the first clinical trial utilizing DCs in cancer patients. Many unanswered questions hamper the development of DC-based vaccines, including the source of DC preparation and protocols for DC generation, activation and loading with tumor antigens, source of tumor antigens, route of vaccine administration and methods of immunomonitoring. Fortunately, in spite of the many obstacles, DC vaccines continue to hold promise for cancer therapy.

Keywords::

• cancer
• clinical trials
• cytokines
• dendritic cells
• immune escape
• immunosuppression
• immunotherapy
• vaccine

Acknowledgements

Some of the studies referred to in this manuscript were, in part, supported by grants from the NCI (2RO1 CA84270 to MRS) and DoD (PC050252 to MRS).

Notes

CTL: Cytotoxic T lymphoctye; DC: Dendritic cell; IFN: Interferon; IL: Interleukin; PBMC: Peripheral blood mononuclear cell; TLR: Toll-like receptor; TNF: Tumor necrosis factor.