PMID- 28133621 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2331-091X (Print) IS - 2331-0928 (Electronic) VI - 3 IP - 4 DP - 2016 TI - Dendritic cell targeting vaccine for HPV-associated cancer. LID - e1482 [pii] AB - 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. FAU - Yin, Wenjie AU - Yin W AD - Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA. FAU - Duluc, Dorothee AU - Duluc D AD - Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA. FAU - Joo, HyeMee AU - Joo H AD - Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA. FAU - Oh, SangKon AU - Oh S AD - Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA. LA - eng GR - RC1 AI087379/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20170115 PL - United States TA - Cancer Cell Microenviron JT - Cancer cell & microenvironment JID - 101647794 PMC - PMC5267343 MID - NIHMS840800 OTO - NOTNLM OT - CD40 OT - Cancer OT - Cross-presentation OT - Dendritic cell OT - HPV OT - Immunotherapy OT - Lectin OT - Vaccine COIS- Conflicting interests The authors declare no conflict of interests except that SO is a named inventor of patents relating to DC targeting that are held by Baylor Research Institute. EDAT- 2017/01/31 06:00 MHDA- 2017/01/31 06:01 PMCR- 2017/01/26 CRDT- 2017/01/31 06:00 PHST- 2017/01/31 06:00 [entrez] PHST- 2017/01/31 06:00 [pubmed] PHST- 2017/01/31 06:01 [medline] PHST- 2017/01/26 00:00 [pmc-release] AID - e1482 [pii] PST - ppublish SO - Cancer Cell Microenviron. 2016;3(4):e1482. Epub 2017 Jan 15.