Dendritic Cell Targeting Vaccine for HPV-Associated Cancer

Abstract

Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients.Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8 + T cells, from the blood of HPV16 + head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16-associated malignancies. Dendritic cells (DCs) are the major antigen presenting cells (APCs) that can efficiently cross-prime antigen-specific CD8 + T cells [1,2] . Such functional specialty in turn makes DCs the ideal cellular targets for the rational design of vaccine against cancers. In line with these notions, Bonifaz et al. demonstrated that antigen targeting to in vivo DCs via DEC-205 using conjugates of anti-DEC-205 and antigen is far more efficient than antigen alone at eliciting antigen-specific cellular immunity [3] .For more than a decade after the initial report on DC targeting vaccines [3] , groups of scientists have been trying to RESEARCH HIGHLIGHTCancer Cell & Microenvironment 2016; 3: e1482. doi: 10.14800/ccm.1482; © 2016 by Wenjie Yin, et al.Page 2 of 6 optimize DC-targeting vaccines by delivering antigens to different DC surface receptors. These receptors include c-type lectins (e.g., DEC205, DC-SIGN, CD207, LOX-1, DC-ASGPR, Dectin-1, DCIR, DCIR2, CLEC6, CLEC9A, and CLEC12A) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][...

Advancing Immunotherapies for HPV-Related Cancers: Exploring Novel Vaccine Strategies and the Influence of Tumor Microenvironment

“…Dendritic cells play a crucial role in immunotherapy strategies due to their ability to mediate and induce both innate and adaptive immune responses [ 233 ]. They are designed to enhance antigen presentation through the activation and expansion of tumor-specific T cells inciting the induction of long-lasting antitumor immunity [ 180 , 234 ]. In addition, some subtypes of DCs acquire exogenous antigens and present them through MHC-II molecules for CD4+ T cells and MHC-I molecules for CD8+ T cells resulting in cross-presentation [ 235 ].…”