自体T细胞活化在B淋巴细胞白血病中的应用

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Therapeutic exploitation of autologous T-cell activation in B-cell lymphoma

T lymphocytes play a critical role in the immune defense against foreign pathogens and cancer. For the past few decades, activating autologous T cells was primarily achieved through vaccination and cytokine stimulation. For native T cells to be activated, T-cell receptors must recognize a peptide that is presented by an antigen-presenting cell through Human Leukocyte Antigen (HLA) classes I and II. In contrast, antibodies, including surface-bound B-cell receptors, can recognize surface antigens independent of HLA restriction. Most antibodies induce anti-tumour response through antibody-dependent cytotoxicity and complement-dependent cytotoxicity. Because most tumour cells are either poor antigen presenters or frequently develop mechanisms to evade immune-cell recognition, investigators developed molecular methods to induce T-cell activation by cell surface proteins, rather than through HLA-restricted peptides. By doing so, a large pool of T cells can be activated by a variety of tumour antigens. One method is to engineer bispecific antibodies that bind to a target antigen on tumour cells, and CD3 on T lymphocytes. Initially, bispecific antibodies consisted of two full antibodies fused at their Fc tails. More recently, smaller molecules were generated to better facilitate tumour site penetration. This review will focus on recent data on the use of engineered chimeric antigen receptor (CAR) T cells and immune checkpoint inhibitors in lymphoma

自体T细胞活化在B淋巴细胞白血病中的应用

T淋巴细胞在抵御外来病原体和癌症的免疫防御中起了关键作用。在过去的几十年中，自体T细胞的活化主要依靠疫苗和细胞因子的刺激来实现。至于本身T细胞的活化，T细胞受体必须识别由抗原提呈细胞通过人类白细胞抗原（HLA）I和II识别一个多肽。相反，抗体，包括表面结合的B细胞受体，可以独立于HLA识别表面抗原。大多数抗体通过抗体依赖的细胞毒作用和补体依赖的细胞毒作用诱导抗肿瘤反应。由于大多数肿瘤细胞有很差的抗原性，而且还会发展出逃避免疫细胞识别的机制，研究者通过分子手段利用细胞表面蛋白诱导T细胞活化，而不是通过HLA限制性肽。通过这些方法，大量的T细胞能够被肿瘤抗原活化。其中一个方法就是改造双抗，能够连接一个靶抗原到肿瘤细胞上，另一个CD3到T细胞。最初的时候，双抗是由两个完整的抗原通过他们的Fc尾部连接。在最近，能够生产出更小的分子，能够更好的促进肿瘤部位的渗透。本文将重点介绍使用嵌合抗原受体修饰的T细胞和免疫检查点抑制剂治疗淋巴瘤。

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