443 An immunotherapy trio in advanced HNSCC for coordinated B and T cell antigen response

Authors

Bernard A Fox, Chiles Research Institute Providence Portland Medical CenterFollow
Tarsem Moudgil, Earle A. Chiles Research Institute, Providence Cancer InstituteFollow
Traci Hilton
Noriko Iwamoto
Christopher Paustian
Adi Mehta
Fridtjof Lund-Johansen
Rachel E Sanborn, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, ORFollow
Richard Bryan Bell, Earle A. Chiles Research Institute, Providence Cancer InstituteFollow
Madeleine Laws
Glenna McDonnell
Yoshinobu Koguchi, Robert W Franz Cancer Center, Earle A Chiles Research Institute, Portland, OR, USAFollow
Carlo Bifulco, Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, ORFollow
Brian D. Piening, Molecular Genomics Laboratory, Providence Portland Medical Center, Portland, OR; Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Cancer Center, Portland, OR.Follow
Carmen Ballesteros-Merino, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.Follow
Shawn M. Jensen, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center and Providence Portland Medical Center, Portland, OregonFollow
Takashi Shimada
Hong-Ming Hu, Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.Follow
Walter Urba, Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213, USA.Follow
Rom Leidner, Earle A. Chiles Research Institute, Providence Cancer InstituteFollow
Marcus Couey, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA; Providence Cancer Institute, Portland, OR, USAFollow

Document Type

Presentation

Publication Date

11-9-2020

Publication Title

Journal of ImmunoTherapy of Cancer

Abstract

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 NCT04470024

Ethics 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.

http://dx.doi.org/10.1136/jitc-2020-SITC2020.0443

Clinical Institute

Cancer

Department

Earle A. Chiles Research Institute

Department

Oncology


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