Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl epitope-activated immune responders: findings from a pilot study.

Background: Dendritic cell (DC)-based and cytokine-induced killer cell (CIK)-based therapy can induce specific antitumor T-cell responses. This clinical pilot study examined the safety, the feasibility, and the outcome of tumor-specific immunotherapy for patients with advanced pancreatic adenocarcinoma.

Methods: Alpha-Gal epitopes were synthesised on pancreatic carcinoma cell membranes with α1,3-galactosyltransferase in vitro. Subsequently, the addition of natural human anti-Gal IgG to the processed membranes resulted in opsonization and effective phagocytosis by DCs, which were co-cultured with newly differentiated CIKs from bone marrow stem cells to generate tumor-specific immune responders ex vivo. Fourteen patients with inoperable stage III/IV pancreatic adenocarcinoma were enrolled in the study; the treatment procedure consisted of injections of DCs and CIKs.

Results: Clinical observation showed that the procedure was safe and lacked serious side effects. Tests showed that 12 patients had strong positive delayed-type IV hypersensitivity to the autologous cancer cell lysate; robust systemic cytotoxicity elicited by interferon (IFN)γ expression by peripheral blood mononuclear cells; and significant increases in CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells in peripheral blood lymphocytes after 3 injections. During the follow up, the percentages of CD3+CD8+, CD3+CD45RO+, and CD3+CD56+ cells returned to the normal range at 6 to 9 months after the third injection and IFNγ expression in the cells stayed at the higher level from the third injection to 24 months after the treatment.

Conclusions: This new tumor-specific immunotherapy is safe, feasible, and has great potential for pancreatic carcinoma treatment.