Reassessing target antigens for adoptive T-cell therapy.
Reassessing target antigens for adoptive T-cell therapy.
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DOI：
10.1038/nbt.2725
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发表时间：
2013-11
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
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作者：
连续性T细胞疗法可以靶向并杀死广泛分布的恶性细胞，从而在黑色素瘤和选定的其他恶性肿瘤中诱导持久的临床应答。然而，许多通常靶向的肿瘤抗原也由健康组织表达，并且如果良性和恶性组织都表达靶抗原，则T细胞不能区分良性和恶性组织。因此，来自T细胞介导的正常组织破坏的自身免疫毒性限制了这种原本有前途的癌症治疗类型的开发和采用。回顾T细胞治疗的独特生物学和最近的临床经验，迫使重新评估传统上从较弱的免疫模式的角度来看的靶抗原。在选择过继性T细胞治疗的靶抗原时，由肿瘤而不是由基本健康组织表达是至关重要的。自身免疫不良事件的风险可以通过使用降低针对非预期靶标中的表位的交叉反应性的机会的策略产生抗原受体来进一步减轻。总的来说，谨慎的靶点选择方法和周到的临床前和临床研究对于这些有前途的治疗方法的持续发展至关重要。
Adoptive T cell therapy can target and kill widespread malignant cells thereby inducing durable clinical responses in melanoma and selected other malignances. However, many commonly targeted tumor antigens are also expressed by healthy tissues, and T cells do not distinguish between benign and malignant tissues if both express the target antigen. As such, autoimmune toxicity from T-cell-mediated destruction of normal tissue has limited the development and adoption of this otherwise promising type of cancer therapy. A review of the unique biology of T-cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities. In selecting target antigens for adoptive T-cell therapy, expression by tumors and not by essential healthy tissues is of paramount importance. The risk of autoimmune adverse events can be further mitigated by generating antigen receptors using strategies that reduce the chance of cross-reactivity against epitopes in unintended targets. In general, a circumspect approach to target selection and thoughtful preclinical and clinical studies are pivotal to the ongoing advancement of these promising treatments.
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通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
DOI：
10.4049/jimmunol.1001775
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chinnasamy N;Wargo JA;Yu Z;Rao M;Frankel TL;Riley JP;Hong JJ;Parkhurst MR;Feldman SA;Schrump DS;Restifo NP;Robbins PF;Rosenberg SA;Morgan RA
通讯作者：
Morgan RA
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
3.2
作者：
Cao, Y;Blohm, D;Karsten, U
通讯作者：
Karsten, U