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.