实体瘤恶性肿瘤的过继细胞疗法:文献回顾与未来挑战。

Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead.

机构信息

Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA

Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA.

出版信息

J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2021-002723.

Abstract

While immune checkpoint inhibitors (ICIs) have ushered in major changes in standards of care for many solid tumor malignancies, primary and acquired resistance is common. Insufficient antitumor T cells, inadequate function of these cells, and impaired formation of memory T cells all contribute to resistance mechanisms to ICI. Adoptive cellular therapy (ACT) is a form of immunotherapy that is rapidly growing in clinical investigation and has the potential to overcome these limitations by its ability to augment the number, specificity, and reactivity of T cells against tumor tissue. ACT has revolutionized the treatment of hematologic malignancies, though the use of ACT in solid tumor malignancies is still in its early stages. There are currently three major modalities of ACT: tumor-infiltrating lymphocytes (TILs), genetically engineered T-cell receptors (TCRs), and chimeric antigen receptor (CAR) T cells. TIL therapy involves expansion of a heterogeneous population of endogenous T cells found in a harvested tumor, while TCRs and CAR T cells involve expansion of a genetically engineered T-cell directed toward specific antigen targets. In this review, we explore the potential of ACT as a treatment modality against solid tumors, discuss their advantages and limitations against solid tumor malignancies, discuss the promising therapies under active investigation, and examine future directions for this rapidly growing field.

摘要

虽然免疫检查点抑制剂 (ICIs) 为许多实体瘤恶性肿瘤的治疗标准带来了重大变化,但原发性和获得性耐药很常见。抗肿瘤 T 细胞数量不足、这些细胞功能不足以及记忆 T 细胞形成受损都会导致对 ICI 的耐药机制。过继细胞疗法 (ACT) 是一种免疫疗法,正在临床研究中迅速发展,并且有可能通过其增加针对肿瘤组织的 T 细胞数量、特异性和反应性来克服这些限制。ACT 已经彻底改变了血液恶性肿瘤的治疗方法,尽管 ACT 在实体瘤恶性肿瘤中的应用仍处于早期阶段。目前有三种主要的 ACT 方式:肿瘤浸润淋巴细胞 (TILs)、基因工程 T 细胞受体 (TCRs) 和嵌合抗原受体 (CAR) T 细胞。TIL 治疗涉及从收获的肿瘤中扩增异质性的内源性 T 细胞群体,而 TCR 和 CAR T 细胞涉及扩增针对特定抗原靶标的基因工程 T 细胞。在这篇综述中,我们探讨了 ACT 作为一种治疗实体瘤的方法的潜力,讨论了它们针对实体瘤恶性肿瘤的优缺点,讨论了正在积极研究的有前途的疗法,并研究了这个快速发展领域的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fde/8311333/17391887e655/jitc-2021-002723f01.jpg

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