Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes targeting multiple myeloma and other plasma cell disorders
Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes targeting multiple myeloma and other plasma cell disorders
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DOI：
10.1111/j.1365-2141.2011.08850.x
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发表时间：
2011-11-01
影响因子：
6.5
通讯作者：
Munshi, Nikhil C.
中科院分区：
文献类型：
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作者：
Bae, Jooeun;Tai, Yu-Tzu;Munshi, Nikhil C.
针对CD138抗原的免疫治疗策略的发展可能代表着多发性骨髓瘤(MM)的一种新的治疗选择。这项研究评估了CD138多肽特异性细胞毒性T淋巴细胞(CTL)的免疫功能，该CTL是用抗MM细胞的HLA-A2特异性CD138表位体外产生的。从CD138抗原的全长蛋白序列中鉴定出一种新的免疫原性CD138(260-268)(GLVGLIFAV)多肽，它能诱导原代CD138(+)MM细胞特异性CTL。多肽诱导的CD138-CTL含有高比例的CD8(+)激活/记忆T细胞，低比例的CD4(+)T细胞和幼稚的CD8(+)T细胞亚群。CTL对MM细胞株表现出HLA-A2限制性杀伤活性和CD138抗原特异性杀伤活性。此外，CD138-CTL能促进骨髓瘤细胞脱颗粒、增殖和分泌干扰素，但对骨髓瘤细胞无明显影响。从骨髓瘤患者分离的原代人类白细胞抗原A2(+)/CD138(+)细胞也证实了CD138-CTL的免疫功能。综上所述，一种新型免疫原性CD138(260-268)(GLVGLIFAV)多肽能够诱导抗原特异性CTL，有望用于多肽疫苗或细胞免疫治疗方案的治疗。
The development of an immunotherapeutic strategy targeting CD138 antigen could potentially represent a new treatment option for multiple myeloma (MM). This study evaluated the immune function of CD138 peptide-specific cytotoxic T lymphocytes (CTL), generated ex vivo using an HLA-A2-specific CD138 epitope against MM cells. A novel immunogenic HLA-A2-specific CD138(260-268) (GLVGLIFAV) peptide was identified from the full-length protein sequence of the CD138 antigen, which induced CTL specific to primary CD138(+) MM cells. The peptide-induced CD138-CTL contained a high percentage of CD8(+) activated/memory T cells with a low percentage of CD4(+) T cell and naive CD8(+) T cell subsets. The CTL displayed HLA-A2-restricted and CD138 antigen-specific cytotoxicity against MM cell lines. In addition, CD138-CTL demonstrated increased degranulation, proliferation and gamma-interferon secretion to HLA-A2(+)/CD138(+) myeloma cells, but not HLA-A2)/CD138(+) or HLA-A2(+)/CD138) cells. The immune functional properties of the CD138-CTL were also demonstrated using primary HLA-A2(+)/CD138(+) cells isolated from myeloma patients. In conclusion, a novel immunogenic CD138(260-268) (GLVGLIFAV) peptide can induce antigen-specific CTL, which might be useful for the treatment of MM patients with peptide-based vaccine or cellular immunotherapy strategies.