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引用次数: 0
摘要
嵌合抗原受体工程化T细胞和双特异性抗体已被证明是治疗各种白血病的有效疗法,而依赖内源性T细胞反应(包括免疫检查点阻断)的模式却未被证明是有益的。这是因为针对突变负荷相对较低的 ALL 和 AML 肿瘤,尤其是儿科肿瘤,缺乏诱导的内源性反应。在这里,我们将讨论儿科白血病中内源性融合和新抗原特异性T细胞反应的鉴定和特征描述,以及通过表位扩散鉴定CAR T细胞疗法期间产生的此类反应的尝试。我们将介绍有效检测这些反应的新方法,以及成功抗肿瘤免疫的 T 细胞特征。
1028 – EXOGENOUS AND ENDOGENOUS IMMUNE TARGETING OF HEMATOLOGICAL MALIGNANCIES
Chimeric antigen receptor-engineered T cells and bispecific antibodies have proven to be effective therapies for a range of leukemias, whereas modalities that rely on endogenous T cell responses including immune checkpoint blockade have not proven as beneficial. This has been attributed to a lack of elicited endogenous responses against relatively low mutation burden ALL and AML tumors, particularly in pediatrics. Here we will discuss the identification and characterization of endogenous fusion- and neoantigen-specific T cell responses in pediatric leukemias, as well as attempts to identify such responses arising during CAR T cell therapies via epitope spreading. Novel methods for efficiently detecting these responses will be described, along with the T cell features that characterize successful anti-tumor immunity.
期刊介绍:
Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.