T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer

被引：1108

作者：

Tran, Eric ^{[1
]}

Robbins, Paul F. ^{[1
]}

Lu, Yong-Chen ^{[1
]}

Prickett, Todd D. ^{[1
]}

Gartner, Jared J. ^{[1
]}

Jia, Li ^{[1
]}

Pasetto, Anna ^{[1
]}

Zheng, Zhili ^{[1
]}

Ray, Satyajit ^{[1
]}

Groh, Eric M. ^{[1
]}

Kriley, Isaac R. ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

机构：

[1] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2016年 / 375卷 / 23期

关键词：

CTLA-4; BLOCKADE; PD-1; TUMOR; IDENTIFICATION; PATIENT; LYMPHOCYTES; SENSITIVITY;

D O I：

10.1056/NEJMoa1609279

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective regression of all seven lung metastases after the infusion of approximately 1.11x10(11) HLA-C*08: 02-restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed on evaluation 9 months after therapy. The lesion was resected and found to have lost the chromosome 6 haplotype encoding the HLA-C*08: 02 class I major histocompatibility complex (MHC) molecule. The loss of expression of this molecule provided a direct mechanism of tumor immune evasion. Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective antitumor immunotherapy against a cancer that expressed mutant KRAS G12D and HLA-C*08: 02.

引用

页码：2255 / 2262

页数：8

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