T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis
T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of Metastatic Colorectal Cancer but Induce Severe Transient Colitis
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DOI：
10.1038/mt.2010.272
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发表时间：
2011-03-01
影响因子：
12.4
通讯作者：
Rosenberg, Steven A.
中科院分区：
文献类型：
--
作者：
Parkhurst, Maria R.;Yang, James C.;Rosenberg, Steven A.
自体T淋巴细胞基因工程表达鼠T细胞受体（TCR）对人类癌胚抗原（CEA）给予3例转移性结直肠癌难治性的标准治疗。所有患者的血清CEA水平均显著降低（74-99%），1例患者的肺和肝转移癌客观消退。然而，在所有3例患者中均诱导了代表剂量限制性毒性的重度一过性炎性结肠炎。本报告代表了第一个例子，客观回归的转移性结直肠癌介导的过继性T细胞转移，并说明了成功使用的TCR，提出了人类白细胞抗原（HLA）转基因小鼠，对人类肿瘤相关抗原。它还强调了少量高亲和力T细胞的破坏力以及使用CEA作为癌症免疫治疗靶点的局限性。
Autologous T lymphocytes genetically engineered to express a murine T cell receptor (TCR) against human carcinoembryonic antigen (CEA) were administered to three patients with metastatic colorectal cancer refractory to standard treatments. All patients experienced profound decreases in serum CEA levels (74-99%), and one patient had an objective regression of cancer metastatic to the lung and liver. However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients. This report represents the first example of objective regression of metastatic colorectal cancer mediated by adoptive T cell transfer and illustrates the successful use of a TCR, raised in human leukocyte antigen (HLA) transgenic mice, against a human tumor associated antigen. It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy.