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Vaccines 2018, 6(3), 54; https://doi.org/10.3390/vaccines6030054

Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis

1
Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA
2
Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
3
Department of Surgery, Boston University School of Medicine, Boston, MA 02118, USA
*
Author to whom correspondence should be addressed.
Received: 13 July 2018 / Revised: 6 August 2018 / Accepted: 6 August 2018 / Published: 10 August 2018
(This article belongs to the Special Issue Therapeutic Vaccines and Cancer Immunotherapy)
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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. View Full-Text
Keywords: intraperitoneal immunotherapy; vaccines; CAR-T cells; ascites; carcinoembryonic antigen; folate receptor α; dendritic cells; peritoneal; metastasis intraperitoneal immunotherapy; vaccines; CAR-T cells; ascites; carcinoembryonic antigen; folate receptor α; dendritic cells; peritoneal; metastasis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Thadi, A.; Khalili, M.; Morano, W.F.; Richard, S.D.; Katz, S.C.; Bowne, W.B. Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis. Vaccines 2018, 6, 54.

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