Combination of cytokine-induced killer and dendritic cells pulsed with antigenic alpha-1,3-galactosyl epitope-enhanced lymphoma cell membrane for effective B-cell lymphoma immunotherapy

摘要

Background aims. Refractory B-cell lymphomas are difficult to successfully treat with current chemotherapeutic regimens; however, immunotherapy may be an effective form of treatment for these patients. Methods. Fourteen refractory lymphoma patients (age, 29-74 y) were enrolled in the trial. alpha-1,3-galactosyl (alpha-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant alpha-1,3-galactosyltransferase (alpha-GT) and neuraminidase to enhance tumor immunogenicity. Subsequent incubation of processed cell membranes with autologous dendritic cells (DCs) in the presence of human serum containing abundant natural anti alpha-Gal immunoglobulin G led to the effective phagocytosis of tumor membranes by DCs. The pulsed DCs and autologous cytokine-induced killer cells were then co-cultured to promote maximum cytotoxicity to lymphoma cells and were infused back into the donor lymphoma patients. Therapeutic responses were assessed by clinical observation, laboratory tests and a computed tomography scan at 6 months after treatment. Results. Complete and partial remission occurred in four and three patients, respectively. The disease status remained unchanged in five patients, and disease progression was observed in two patients. No serious side effects or autoimmune diseases were observed in any participants. Serum lactate dehydrogenase and beta-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-gamma expression in peripheral blood mononuclear cells after treatment (P < 0.001). The number of peripheral immune effector cells (CD3(+)/CD4(+), CD8(+)/CD28(+) and CD16(+)/CD56(+) cells) increased significantly (P < 0.05) 3 months after treatment. Conclusions. Lymphoma cell specific alpha-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma.