New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibody-drug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CAR-T cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CAR-T cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a “do-not-eat-me” immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR- T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.

中文翻译：

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CAR-T“活体药物”、免疫检查点抑制剂和精准医疗：癌症治疗的新时代。

单克隆抗体、双特异性 T 细胞接合剂和抗体药物偶联物的设计和制造方面的新进展使抗体导向药物的功效更强大，毒性更小。小分子抑制剂现在通常用作多种癌症的口服靶向药物。PD1和PD-L1作为T细胞阴性免疫检查点的发现引发了现代癌症免疫治疗的革命。针对 PD1、PD-L1 或 CTLA-4 的多种药物作为免疫检查点抑制剂 (ICIs) 被广泛应用，可减轻对免疫调节机制的抑制，并导致 IV 期肺癌等一度高度难治性癌症的免疫消融。Tisagenlecleucel 和 axicabtagene ciloleucel 是两种获批的靶向 CD19 的嵌合抗原受体 (CAR) T 细胞产品。多个针对 B 细胞成熟抗原 (BCMA) 的 CAR-T 细胞平台正在进行针对难治性和/或复发性多发性骨髓瘤的积极临床试验。更多的靶标，如 CLL-1、EGFR、NKG2D 和间皮素，正在针对白血病和实体瘤的 CAR-T 细胞试验进行研究。越来越多的新型药物正在研究中，以针对癌症内在的致癌途径以及免疫检查点。其中一个例子是针对巨噬细胞上的 CD47，它代表着“不要吃我”的免疫检查点。TCR-T 细胞、TCR 样抗体、癌症疫苗和溶瘤病毒也推动了当前癌症医学的发展。