用于胰腺癌的新抗原 T 细胞受体基因治疗。
Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer.
机构信息
From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.).
出版信息
N Engl J Med. 2022 Jun 2;386(22):2112-2119. doi: 10.1056/NEJMoa2119662.
Abstract
A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2×10 autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02-restricted T-cell receptors (TCRs) targeting mutant KRAS G12D expressed by the tumors. The patient had regression of visceral metastases (overall partial response of 72% according to the Response Evaluation Criteria in Solid Tumors, version 1.1); the response was ongoing at 6 months. The engineered T cells constituted more than 2% of all the circulating peripheral-blood T cells 6 months after the cell transfer. In this patient, TCR gene therapy targeting the KRAS G12D driver mutation mediated the objective regression of metastatic pancreatic cancer. (Funded by the Providence Portland Medical Foundation.).
摘要
一名患有进行性转移性胰腺癌的患者接受了单次输注 16.2×10 个自体 T 细胞的治疗，这些 T 细胞经过基因工程改造，能够克隆表达两种同种异体 HLA-C*08:02 限制性 T 细胞受体（TCRs），靶向肿瘤表达的突变 KRAS G12D。患者的内脏转移得到了缓解（根据实体瘤反应评价标准，1.1 版，总体部分缓解率为 72%）；在 6 个月时反应仍在持续。在细胞转移后 6 个月时，工程化 T 细胞构成了超过所有循环外周血 T 细胞的 2%。在这名患者中，针对 KRAS G12D 驱动突变的 TCR 基因治疗介导了转移性胰腺癌的客观缓解。（由普罗维登斯波特兰医疗基金会资助）。
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