The First 1000 Dendritic Cell Vaccinees

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that have the ability to stimulate primary T cell antitumor immune responses in animals and humans. Since the first published clinical trial of dendritic cell vaccination in 1995, 98 studies describing more than 1000 vaccinees have been published in peer-reviewed medical journals or presented at the annual meetings of the American Society for Clinical Oncology, the American Association of Cancer Research, or the American Society of Hematology. Trials have been performed in 15 countries. Trials included patients with more than two dozen tumor types; most trials studied patients with malignant melanoma, prostate cancer, colorectal carcinoma, or multiple myeloma, using autologous DCs pulsed with synthetic antigens or idiotype antibodies. The DC vaccines were also prepared by pulsing DCs with tumor lysates or RNA, by transfection with tumor DNA, or by creating tumor cell/DC fusions. Various approaches to vaccine cell numbers, length of vaccine program, site of vaccination, frozen preservation of vaccine, and use of a maturations step for DCs were used. Adverse effects associated with DC vaccination were uncommon; most were mild and self-limited and none were serious. Clinical responses were observed in approximately half the trials. The DC vaccination may provide a safe approach to cancer immunotherapy that can overcome the limited reach and immunogenicity of peptide vaccines.

Targeting tumors with LIGHT to generate metastasis-clearing immunity

“…Despite relative simplicity and safety, vaccine treatments have shown very limited success [89]. Although the generation in vivo of antitumor T cells in vaccinated patients could be demonstrated by techniques such as tetramer or ELISpot assays [90][91][92], clinical responses observed from these trials were few [89]. This was consistent with the finding in murine models that the presence of even large numbers of antigen-specific T cells is insufficient to mediate tumor regression [14,93].…”

Visualizing dendritic cell migration within the skin

“…Based on advances in the generation of DCs for therapeutic purposes, a number of clinical trials over the past decade have employed DC vaccination as a treatment for a variety of cancers, particularly melanoma (Lesterhuis et al 2008;Ridgway 2003). Typically, this involves the in vitro generation of DCs from blood monocytes or CD34 + precursor cells using cytokines such as GM-CSF and IL-4, followed by activation using various inXammatory mediators and antigenic loading prior to intradermal (i.d.)…”

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

“…2 Despite the widespread use of DCs in tumor vaccination protocols, 3 the limited clinical success of DC vaccines necessitates new methodologies for improving DC vaccine potency. 4 Several methods for manipulating antigen-presenting DCs have been developed in experimental studies and applied in clinical trials. As T-cell priming is drastically affected by the expression levels of costimulatory molecules on DCs, many DC-based vaccine strategies are focused on manipulating the DC activation state.…”