Chimeric Antigen Receptor-T Cell and Oncolytic Viral Therapies for Gastric Cancer and Peritoneal Carcinomatosis of Gastric Origin: Path to Improving Combination Strategies

Author:

Chen Courtney1,Jung Audrey1,Yang Annie1,Monroy Isabel2,Zhang Zhifang1,Chaurasiya Shyambabu1ORCID,Deshpande Supriya1,Priceman Saul23,Fong Yuman1,Park Anthony K.123ORCID,Woo Yanghee13

Affiliation:

1. Department of Surgery, City of Hope, Duarte, CA 91010, USA

2. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA

3. Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA

Abstract

Precision immune oncology capitalizes on identifying and targeting tumor-specific antigens to enhance anti-tumor immunity and improve the treatment outcomes of solid tumors. Gastric cancer (GC) is a molecularly heterogeneous disease where monoclonal antibodies against human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death 1 (PD-1) combined with systemic chemotherapy have improved survival in patients with unresectable or metastatic GC. However, intratumoral molecular heterogeneity, variable molecular target expression, and loss of target expression have limited antibody use and the durability of response. Often immunogenically “cold” and diffusely spread throughout the peritoneum, GC peritoneal carcinomatosis (PC) is a particularly challenging, treatment-refractory entity for current systemic strategies. More adaptable immunotherapeutic approaches, such as oncolytic viruses (OVs) and chimeric antigen receptor (CAR) T cells, have emerged as promising GC and GCPC treatments that circumvent these challenges. In this study, we provide an up-to-date review of the pre-clinical and clinical efficacy of CAR T cell therapy for key primary antigen targets and provide a translational overview of the types, modifications, and mechanisms for OVs used against GC and GCPC. Finally, we present a novel, summary-based discussion on the potential synergistic interplay between OVs and CAR T cells to treat GCPC.

Funder

Department of Defense Idea Award

Alfred E. Mann Charities

Natalie and David Roberts family

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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