TY - JOUR T1 - 443 An immunotherapy trio in advanced HNSCC for coordinated B and T cell antigen response JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer SP - A269 LP - A270 DO - 10.1136/jitc-2020-SITC2020.0443 VL - 8 IS - Suppl 3 AU - Bernard Fox AU - Tarsem Moudgil AU - Traci Hilton AU - Noriko Iwamoto AU - Christopher Paustian AU - Adi Mehta AU - Fridtjof Lund-Johansen AU - Rachel Sanborn AU - Bryan Bell AU - Madeleine Laws AU - Glenna McDonnell AU - Yoshinobu Koguchi AU - Carlo Bifulco AU - Brian Piening AU - Carmen Ballesteros Merino AU - Shawn Jensen AU - Takashi Shimada AU - Hong-Ming Hu AU - Walter Urba AU - Rom Leidner AU - Marcus Couey AU - Marcus Couey Y1 - 2020/11/01 UR - http://jitc.bmj.com/content/8/Suppl_3/A269.abstract N2 - Background Outcomes for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are dismal and responses to anti-PD-1 appear best in tumors with PD-1+ T cells in proximity to PD-L1+ cells, arguing that improved outcome is associated with a pre-existing anti-cancer immune response. Based on this, we hypothesize that vaccines which prime and/or expand T cells to a spectrum of antigens overexpressed by HNSCC combined with T cell agonists, like anti-GITR, that provide costimulatory signals will improve the anti-PD-1 response rates. We have developed a cancer vaccine, DPV-001, that contains more than 300 proteins for genes overexpressed by HNSCC, encapsulated in a CLEC9A-targeted microvesicle and containing TLR/NOD agonists and DAMPs. Recently, we reported that combining anti-GITR + vaccine + anti-PD-1 augmented therapeutic efficacy in a preclinical model and now plan a phase 1b trial of this combination in patients with advanced HNSCC.Methods Sera from patients receiving DPV-001 as adjuvant therapy for definitively treated NSCLC, were analyzed for IgG responses to human proteins by MAP bead arrays and results compared to TCGA gene expression data sets for HNSCC. HNSCC cell lines were evaluated by RNASeq and peptides were eluted from HLA, analyzed by mass spectroscopy and correlated against MAP bead arrays and TCGA data sets. Tumor-reactive T cells from a vaccinated patient were enriched and expanded, and used in cytokine release assay (CRA) against autologous NSCLC and partially HLA matched allogeneic HNSCC cell lines.Results Patients receiving DPV-001 (N=13) made 147 IgG responses to at least 70 proteins for genes overexpressed by HNSCC. Preliminary evaluation of the HNSCC peptidome against the results of MAP bead array identify antigens that are target of a humoral immune response. Additionally, tumor-reactive T cells from DPV-001 vaccinated patient recognize two partially HLA-matched HNSCC targets, but not a mis-matched target.Conclusions Recent observations from our lab and others have correlated IgG Ab responses with T cell responses to epitopes of the same protein. Based on the data summarized above, we hypothesize that we have induced T cell responses against a broad spectrum of shared cancer antigens that are common among adenocarcinomas and squamous cell cancers. Our planned clinical trial will vaccinate and boost the induced responses by costimulation with anti-GITR and then sequence in delayed anti-PD-1 to relieve checkpoint inhibition. MAP bead arrays and the peptidome library generated above will be used to assess anti-cancer B and T cell responses.Trial Registration NCT04470024Ethics Approval The original clinical trial was approved by the Providence Portland Medical Center IRB, approval # 13-046. The proposed clinical trial has not yet been reviewed by the IRB. ER -