Cancer immunotherapy for pancreatic cancer utilizing α-gal epitope/natural anti-Gal antibody reaction

Masahiro Tanemura, Eiji Miyoshi, Hiroaki Nagano, Hidetoshi Eguchi, Katsuyoshi Matsunami, Kiyomi Taniyama, Nobutaka Hatanaka, Hiroki Akamatsu, Masaki Mori, Yuichiro Doki

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9 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis of all malignancies and is largely resistant to standard therapy. Novel treatments against PDAC are desperately needed. Anti-Gal is the most abundant natural antibody in humans, comprising about 1% of immunoglobulins and is also naturally produced in apes and Old World monkeys. The anti-Gal ligand is a carbohydrate antigen called "α-gal epitopes" with the structure Galα1-3Galβ1-4GlcNAc-R. These epitopes are expressed as major carbohydrate antigens in non-primate mammals, prosimians, and New World monkeys. Anti-Gal is exploited in cancer vaccines to increase the immunogenicity of antigen-presenting cells (APCs). Cancer cells or PDAC tumor lysates are processed to express α-gal epitopes. Vaccination with these components results in in vivo opsonization by anti-Gal IgG in PDAC patients. The Fc portion of the vaccine-bound anti-Gal interacts with Fcγ receptors of APCs, inducing uptake of the vaccine components, transport of the vaccine tumor membranes to draining lymph nodes, and processing and presentation of tumor-associated antigens (TAAs). Cancer vaccines expressing α-gal epitopes elicit strong antibody production against multiple TAAs contained in PDAC cells and induce activation of multiple tumor-specific T cells. Here, we review new areas of clinical importance related to the α-gal epitope/anti-Gal antibody reaction and the advantages in immunotherapy against PDAC.

Original languageEnglish
Pages (from-to)11396-11410
Number of pages15
JournalWorld Journal of Gastroenterology
Volume21
Issue number40
DOIs
Publication statusPublished - Oct 28 2015

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Tanemura, M., Miyoshi, E., Nagano, H., Eguchi, H., Matsunami, K., Taniyama, K., Hatanaka, N., Akamatsu, H., Mori, M., & Doki, Y. (2015). Cancer immunotherapy for pancreatic cancer utilizing α-gal epitope/natural anti-Gal antibody reaction. World Journal of Gastroenterology, 21(40), 11396-11410. https://doi.org/10.3748/wjg.v21.i40.11396