Oelke Mathias, Maus Marcela V, Didiano Dominic, June Carl H, Mackensen Andreas, Schneck Jonathan P
Department of Pathology & Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Nat Med. 2003 May;9(5):619-24. doi: 10.1038/nm869. Epub 2003 Apr 21.
Adoptive immunotherapy holds promise as a treatment for cancer and infectious diseases, but its development has been impeded by the lack of reproducible methods for generating therapeutic numbers of antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs). As a result, there are only limited reports of expansion of antigen-specific CTLs to the levels required for clinical therapy. To address this issue, artificial antigen-presenting cells (aAPCs) were made by coupling a soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) and CD28-specific antibody to beads. HLA-Ig-based aAPCs were used to induce and expand CTLs specific for cytomegalovirus (CMV) or melanoma. aAPC-induced cultures showed robust antigen-specific CTL expansion over successive rounds of stimulation, resulting in the generation of clinically relevant antigen-specific CTLs that recognized endogenous antigen-major histocompatibility complex complexes presented on melanoma cells. These studies show the value of HLA-Ig-based aAPCs for reproducible expansion of disease-specific CTLs for clinical approaches to adoptive immunotherapy.
过继性免疫疗法有望成为治疗癌症和传染病的方法，但其发展受到阻碍，因为缺乏可重复的方法来产生治疗所需数量的抗原特异性CD8(+) 细胞毒性T淋巴细胞（CTL）。因此，仅有有限的报道称抗原特异性CTL能扩增到临床治疗所需的水平。为解决这一问题，通过将可溶性人白细胞抗原-免疫球蛋白融合蛋白（HLA-Ig）和CD28特异性抗体偶联到珠子上制备了人工抗原呈递细胞（aAPC）。基于HLA-Ig的aAPC被用于诱导和扩增针对巨细胞病毒（CMV）或黑色素瘤的CTL。aAPC诱导的培养物在连续几轮刺激中显示出强大的抗原特异性CTL扩增，从而产生了临床上相关的抗原特异性CTL，这些CTL能够识别黑色素瘤细胞上呈现的内源性抗原-主要组织相容性复合体复合物。这些研究表明基于HLA-Ig的aAPC对于可重复扩增疾病特异性CTL以用于过继性免疫疗法的临床应用具有价值。
