美国波特兰普罗维登斯癌症中心Earle A. Chiles研究所Eric Tran和Rom Leidner团队研究了胰腺癌患者接受新抗原T细胞受体基因治疗的效果。该项研究成果发表在2022年6月1日出版的《新英格兰医学杂志》上。

1例进展性转移性胰腺癌患者接受16.2×10⁹自体T细胞单次输注治疗，这些T细胞经过基因工程处理，可克隆表达两种靶向肿瘤表达的突变体KRAS G12D的异基因HLA-C*08:02限制性T细胞受体（TCRs）。

患者内脏转移消退（根据实体瘤缓解评价标准1.1版，总部分缓解率为72%）；在6个月时，这种缓解仍然持续。细胞移植6个月后，工程化T细胞占循环外周血T细胞总数的2%以上。

研究结果表明，在该患者中，靶向KRAS G12D驱动基因突变的TCR基因治疗介导了转移性胰腺癌的客观回归。

附：英文原文

Title: Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer

Author: Rom Leidner, M.D.,, Nelson Sanjuan Silva, B.S.,, Huayu Huang, M.S.,, David Sprott, B.S.,, Chunhong Zheng, Ph.D.,, Yi-Ping Shih, Ph.D.,, Amy Leung, B.S.,, Roxanne Payne, M.N.,, Kim Sutcliffe, B.S.N.,, Julie Cramer, M.A.,, Steven A. Rosenberg, M.D., Ph.D.,, Bernard A. Fox, Ph.D.,, Walter J. Urba, M.D., Ph.D.,, and Eric Tran, Ph.D.

Issue&Volume: 2022-06-01

Abstract:

A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2×109 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.

DOI: NJ202206023862208

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2119662