Anti-Gal-mediated targeting of human B lymphoma cells to antigen-presenting cells: a potential method for immunotherapy using autologous tumor cells.
Anti-Gal-mediated targeting of human B lymphoma cells to antigen-presenting cells: a potential method for immunotherapy using autologous tumor cells.
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发表时间：
2005
期刊：
影响因子：
10.1
通讯作者：
O. Manches;J. Plumas;G. Lui;L. Chaperot;J. Molens;J. Sotto;J. Bensa;U. Galili
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文献类型：
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作者：
O. Manches;J. Plumas;G. Lui;L. Chaperot;J. Molens;J. Sotto;J. Bensa;U. Galili
背景和结论B淋巴瘤患者在完成标准化疗和放疗后残留的残留肿瘤细胞可以通过刺激肿瘤特异性T淋巴细胞的主动免疫治疗来根除。放射性自体淋巴瘤细胞表达肿瘤相关抗原（TAA），可以作为一个潜在的肿瘤疫苗，只要他们有效地针对抗原呈递细胞（APC）。我们建议利用天然的抗Gal抗体，以便将肿瘤细胞靶向接种到APC。抗Gal占人血清中IgG的1%，并与α-gal表位（Galalpha 1 - 3GlcNAc 1 -4GlcNAc-R）特异性相互作用。设计与方法利用重组糖基化酶α 1，3-半乳糖基转移酶（α 1，3GT）在原代淋巴瘤细胞膜上体外合成α-gal表位。通过纯化的抗Gal抗体调理处理的肿瘤细胞，并研究APC（包括单核细胞衍生的巨噬细胞和树突细胞）的摄取（吞噬作用）。通过肿瘤特异性CD 8 + T细胞系的活化来测量吞噬处理的MHC-I阴性淋巴瘤细胞后肿瘤抗原的交叉呈递。结果我们证明了在使用重组酶α 1，3 GT后，在新鲜分离的各种类型的B淋巴瘤细胞上α-gal表位的合成。随后，抗Gal抗体与从头合成的巨噬细胞表位结合，调理这些肿瘤细胞，通过Fc γ R1（CD 64）介导的吞噬作用，使其被巨噬细胞和树突状细胞有效摄取。此外，抗Gal介导的吞噬作用导致树突状细胞交叉呈递TAA。解释和结论：本研究表明，用经辐照处理以表达α-半乳糖抗原表位的自体淋巴瘤细胞进行免疫接种将导致抗半乳糖介导的自体肿瘤疫苗体内靶向APC。
BACKGROUND AND OBJECTIVES The residual tumor cells remaining after completion of standard chemotherapy and radiation treatment in B lymphoma patients, may be eradicated by active immunotherapy that stimulates tumor-specific T lymphocytes. Irradiated autologous lymphoma cells expressing tumor-associated antigens (TAA) may serve as a potential tumor vaccine, provided that they are effectively targeted to the antigen-presenting cells (APC). We propose exploiting the natural anti-Gal antibody in order to target vaccinating tumor cells to APC. Anti-Gal constitutes 1% of IgG in human serum and interacts specifically with the alpha-gal epitope (Galalpha1-3Galphalbeta1-4GlcNAc-R). DESIGN AND METHODS Alpha-gal epitopes were synthesized in vitro on the membrane of primary lymphoma cells by using the recombinant glycosylation enzyme alpha1,3galactosyltransferase (alpha1,3GT). Processed tumor cells were opsonized by purified anti-Gal antibodies and studied for uptake (phagocytosis) by APC including monocyte-derived macrophages and dendritic cells. Cross-presentation of tumor antigens after phagocytosis of processed MHC-I negative lymphoma cells was measured by activation of a tumor-specific CD8+ T-cell line. RESULTS We demonstrate synthesis of alpha-gal epitopes on freshly isolated B lymphoma cells of various types following the use of the recombinant enzyme alpha1,3GT. The subsequent binding of anti-Gal to the de novo synthesized alphagal epitopes opsonizes these tumor cells for effective uptake by macrophages and dendritic cells, through phagocytosis mediated by FcgammaR1 (CD64). Moreover, anti-Gal-mediated phagocytosis resulted in cross-presentation of TAA by dendritic cells. INTERPRETATION AND CONCLUSIONS This study suggests that immunization with irradiated autologous lymphoma cells processed to express alpha-gal epitopes will result in anti-Gal-mediated, in vivo targeting of the autologous tumor vaccine to APC.