Cancers eventually kill hosts even when infiltrated by cancer-specific T cells. We examined whether cancer-specific T cell receptors of CD4 + T cells (CD4TCRs) from tumor-bearing hosts can be exploited for adoptive TCR therapy. We focused on CD4TCRs targeting an autochthonous mutant neoantigen that is only presented by stroma surrounding the MHC class II–negative cancer cells. The 11 most common tetramer-sorted CD4TCRs were tested using TCR-engineered CD4 + T cells. Three TCRs were characterized by convergent recombination for which multiple T cell clonotypes differed in their nucleotide sequences but encoded identical TCR α and β chains. These preferentially selected TCRs destroyed tumors equally well and halted progression through reprogramming of the tumor stroma. TCRs represented by single T cell clonotypes were similarly effective only if they shared CDR elements with preferentially selected TCRs in both α and β chains. Selecting candidate TCRs on the basis of these characteristics can help identify TCRs that are potentially therapeutically effective.

中文翻译：

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具有收敛 TCR 重组的 CD4 + T 细胞在过继治疗中重编程基质并阻止肿瘤进展


即使被癌症特异性 T 细胞浸润，癌症最终也会杀死宿主。我们检查了来自荷瘤宿主的 CD4 + T 细胞 （CD4TCR） 的癌症特异性 T 细胞受体是否可用于过继性 TCR 治疗。我们专注于靶向本土突变新抗原的 CD4TCR，该抗原仅由 MHC II 类阴性癌细胞周围的基质呈现。使用 TCR 工程改造的 CD4 + T 细胞对 11 种最常见的四聚体分选 CD4TCR 进行了测试。3 个 TCRs 以收敛重组为特征，其中多个 T 细胞克隆型的核苷酸序列不同，但编码相同的 TCR α 和 β 链。这些优先选择的 TCR 同样有效地破坏了肿瘤，并通过对肿瘤基质的重编程来阻止进展。由单个 T 细胞克隆型代表的 TCR 只有在 α 链和 β 链中与优先选择的 TCR 共享 CDR 元件时，才具有类似的有效性。根据这些特征选择候选 TCR 有助于识别可能具有治疗效果的 TCR。