Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor-Based Cellular Therapy.
Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor-Based Cellular Therapy.
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DOI：
10.1146/annurev-cancerbio-061521-082114
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发表时间：
2023
影响因子：
7.7
通讯作者：
Greenberg, Philip D.
中科院分区：
文献类型：
--
作者：
Martinov, Tijana;Greenberg, Philip D.
T细胞对肿瘤特异性新抗原的反应性可以驱动内源性和治疗诱导的抗肿瘤免疫。然而，大多数肿瘤特异性新抗原对每个患者都是独特的（私人），靶向它们需要个性化治疗。新抗原的较小子集包括跨越致癌驱动因子和肿瘤抑制因子中的复发突变热点、易位或基因融合的表位，以及由病毒致癌蛋白产生的表位。这些抗原可能在患者（公众）之间共享，在肿瘤内均匀表达，并且是癌细胞存活和适应性所需的。尽管这些公共新抗原中的有限数量是天然免疫原性的，但最近的研究证实了它们的临床实用性。在这篇综述中，我们强调了利用现成的T细胞受体工程化T细胞靶向突变型KRAS、突变型p53和致癌病毒表位的努力。我们还讨论了实现更有效的T细胞疗法的挑战和策略，特别是在实体瘤的背景下。
T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers and tumor suppressors, as well as epitopes that arise from viral oncogenic proteins. Such antigens are likely to be shared across patients (public), uniformly expressed within a tumor, and required for cancer cell survival and fitness. Although a limited number of these public neoantigens are naturally immunogenic, recent studies affirm their clinical utility. In this review, we highlight efforts to target mutant KRAS, mutant p53, and epitopes derived from oncogenic viruses using T cells engineered with off-the-shelf T cell receptors. We also discuss the challenges and strategies to achieving more effective T cell therapies, particularly in the context of solid tumors.
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通讯作者：
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