Effect of immune cells induced and differentiated by umbilical cord blood mononuclearcells on immune function of patients with small cell lung cancer / 中国肿瘤生物治疗杂志

@#Objective: To evaluate the effect of immune cells induced and differentiated by umbilical cord blood mononuclear cells (UCMCs) on the immune function of patients with small cell lung cancer (SCLC). Methods: Ninety patients with SCLC, who were admitted to the Affiliated Hospitalof InnerMongolia Medical University from January 2012 to December 2015, were randomly divided into control group (45 patients, EP regimen), study group (45 patients, EP regimen+UCMC-induced and differentiated immune cells). The study group of patients received immune cell treatment 3-5 d after chemotherapy ([1-3]×1010cells/treatment), 30 d for a cycle. The changes in T cell subsets, IFN-γ, IL-2, IL-10 and TGF-β1 in peripheral blood of patients were observed by flow cytometry at pre-treatment and 12 weeks post-treatment. Life quality and adverse events of patients were evaluated. Results: The study group, 15 cases achieved CR, 25 cases of PR and 5 cases of SD. The percent of T cell subsets in the study group was significantly higher than that in the control group (P<0.01), and the time of return to normal level was obviously shorter (P<0.05). The serum level of inflammatory cytokine IFN-γ increased or exceeded the normal range in 80.9% patients, and IL-10 and TGF-β1 levels were significantly decreased as compared with pretreatment (P<0.05). The quality of life was obviously better than that of the control group (P<0.05). Conclusion: Immune cells induced and differentiated by UCMCs can promote the recovery of immune function of patients with SCLC.

Immunity Enhancement in Immunocompromised Gastrointestinal Cancer Patients with Allogeneic Umbilical Cord Blood Mononuclear Cell Transfusion.

Objectives. In order to enhance the immunity of cancer patients to prevent relapse or to prolong survival time, umbilical cord blood mononuclear cells (UCMCs) were transplanted to cancer patients. Patients and Methods. UCMCs were transfused to 63 immunocompromised gastrointestinal cancer patients with nonmyeloablative (NMA) conditioning regimen. Results. The clinical study showed that the number of both T and B cells increased much more rapidly after transfusion of UCMCs than that of the control group without transplantation (p < 0.01). Proinflammation cytokines IFNγ and TNFα in serum increased to or above the normal range in 80.9% of patients at 12 weeks after UCMC transfusion. However, they recovered to the normal range in 21.7% of patients at the same time point in the control group only. In addition, the clinical investigation also showed that the transfusion of UCMC increased stable disease (SD) and reduced progressive disease (PD) significantly (p < 0.01); however, it did not have significant effects on complete response (CR), partial response (PR), or mortality rates compared with the control group (p > 0.05). Conclusions. UCMCs have powerful repairing effects on damaged cells and tissues and may reconstruct the impaired immunity. Transfusion of UCMCs could reconstruct the immunity of cancer patients with immunosuppression.

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

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. α-1,3-galactosyl (α-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant α-1,3-galactosyltransferase (α-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-α-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 ß2-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ 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 α-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma.

Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft.

BACKGROUND: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. METHODS: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. RESULTS: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-ß1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. CONCLUSIONS: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft.