Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis

Abstract

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM.

STING activation normalizes the intraperitoneal vascular-immune microenvironment and suppresses peritoneal carcinomatosis of colon cancer

“…2 3 Local and systemic therapies, including immunotherapies, show limited efficacy, making PCCC a major therapeutic challenge that hampers the survival and quality of life of patients with colon cancer. [3][4][5][6] The progression of PCCC is promoted by robust tumor angiogenesis, which generates tortuous and chaotic networks of neovessels. 7 8 Because these immature vessels are loosely connected and lack adequate pericyte coverage, they are hyperpermeable.…”

Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecular Characterization and Biomarkers

“…In addition, diagnostic or predictive biomarkers of PD might help guide personalized treatment. Intraperitoneal immunotherapy such as intraperitoneal infusion of chimeric antigen receptor (CAR)-T cells has shown promising results in preclinical studies [137,138]. There are ongoing phase 1 and 2 clinical trials aiming to evaluate the safety and efficacy of CAR-T cells targeting EpCAM (NCT03563326), CEA (NCT02349724) or mesothelin (NCT03941626) in treating advanced GC.…”

Therapeutic Vaccines and Cancer Immunotherapy

“…After vector design, research is focused on strategies of vaccine delivery and combinatorial approaches to build-on the immune responses initiated by the vaccines. As an emerging strategy for targeted delivery of therapeutics, Thadi et al describe an interesting approach of intraperitoneal immunotherapy for metastasis of peritoneum in their review [ 15 ]. They discuss how, despite of being a lethal diagnosis, peritoneal metastasis has an improved chance of positive outcomes due to targeted delivery, made possible by intraperitoneal immunotherapy.…”