Immunotherapy for Pancreatic Cancer: Clinical Relevance of α-gal Epitope/Natural Anti-gal Antibody Reaction
Pp. 112-125 (14)
Masahiro Tanemura, Eiji Miyoshi, Hiroaki Nagano, Kiyomi Taniyama, Masaki Mori and Yuichiro Doki
Pancreatic cancer remains lethal and most are resistant to traditional
therapies. New therapeutic approaches, such as immunotherapy are in urgent demand.
Anti-Gal antibody (Ab) is known as the most abundant natural Ab in humans, and the
anti-Gal ligand called “α-gal epitopes” with the structure Galα1-3Galβ1-4GlcNAc-R is
expressed as a major carbohydrate antigen. Pancreatic cancer cells or their lysate may
express α-gal epitopes. Subsequent vaccination with such processed cell membranes
result in in vivo opsonization by anti-Gal IgG in cancer patients. The interaction of the
Fc portion of the vaccine-bound anti-Gal Ab with Fc cγ receptors of APC induces an
effective uptake of the vaccinating tumor cell membranes by the APC, followed by the
effective transport of the vaccinating cancer membranes to the regional lymph nodes,
and processing and presentation of the cancer-associated antigens. Activation of
cancer-specific lymphocytes elicits an immune response to eradicate the residual cancer
cells that remain after completion of standard therapy in some patients. This review focuses on this unique antigen/antibody system (α-gal epitope/natural anti-Gal Ab) and
shows advances in immunotherapy for pancreatic cancer.
3 Galactosyltransferase, α-1, α-gal epitopes, Immunotherapy,
Pancreatic cancer, Universal vaccine.
Department of Surgery, Osaka Police Hospital, 10-31 Kitayamacho Tennouji-ku, Osaka, 543-0035, Japan.