Ochi Toshiki, Fujiwara Hiroshi, Yasukawa Masaki
Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
J Biomed Biotechnol. 2010;2010:521248. doi: 10.1155/2010/521248. Epub 2010 May 5.
The last decade has seen great strides in the field of cancer immunotherapy, especially the treatment of melanoma. Beginning with the identification of cancer antigens, followed by the clinical application of anti-cancer peptide vaccination, it has now been proven that adoptive T-cell therapy (ACT) using cancer antigen-specific T cells is the most effective option. Despite the apparent clinical efficacy of ACT, the timely preparation of a sufficient number of cancer antigen-specific T cells for each patient has been recognized as its biggest limitation. Currently, therefore, attention is being focused on ACT with engineered T cells produced using cancer antigen-specific T-cell receptor (TCR) gene transfer. With regard to human leukemia, ACT using engineered T cells bearing the leukemia antigen-specific TCR gene still remains in its infancy. However, several reports have provided preclinical data on TCR gene transfer using Wilms' tumor gene product 1 (WT1), and also preclinical and clinical data on TCR gene transfer involving minor histocompatibility antigen, both of which have been suggested to provide additional clinical benefit. In this review, we examine the current status of anti-leukemia ACT with engineered T cells carrying the leukemia antigen-specific TCR gene, and discuss the existing barriers to progress in this area.
过去十年间，癌症免疫治疗领域取得了巨大进展，尤其是黑色素瘤的治疗。从癌症抗原的鉴定开始，接着是抗癌肽疫苗的临床应用，现在已经证明，使用癌症抗原特异性T细胞的过继性T细胞疗法（ACT）是最有效的选择。尽管ACT具有明显的临床疗效，但为每位患者及时制备足够数量的癌症抗原特异性T细胞已被认为是其最大的局限性。因此，目前的注意力集中在使用通过癌症抗原特异性T细胞受体（TCR）基因转移产生的工程化T细胞进行的ACT上。关于人类白血病，使用携带白血病抗原特异性TCR基因的工程化T细胞进行的ACT仍处于起步阶段。然而，有几份报告提供了关于使用威尔姆斯瘤基因产物1（WT1）进行TCR基因转移的临床前数据，以及关于涉及次要组织相容性抗原的TCR基因转移的临床前和临床数据，这两者都被认为可能带来额外的临床益处。在本综述中，我们研究了携带白血病抗原特异性TCR基因的工程化T细胞进行抗白血病ACT的现状，并讨论了该领域进展中存在的障碍。
