Department of Biochemistry, College of Medicine, University of Ha'il, Ha'il 81411, Saudi Arabia.
Medical and Diagnostic Research Centre, University of Ha'il, Hail 55473, Saudi Arabia.
Int J Oncol. 2023 Dec;63(6). doi: 10.3892/ijo.2023.5578. Epub 2023 Oct 13.
Cancer is the primary and one of the most prominent causes of the rising global mortality rate, accounting for nearly 10 million deaths annually. Specific methods have been devised to cure cancerous tumours. Effective therapeutic approaches must be developed, both at the cellular and genetic level. Immunotherapy offers promising results by providing sustained remission to patients with refractory malignancies. Genetically modified T‑lymphocytic cells have emerged as a novel therapeutic approach for the treatment of solid tumours, haematological malignancies, and relapsed/refractory B‑lymphocyte malignancies as a result of recent clinical trial findings; the treatment is referred to as chimeric antigen receptor T‑cell therapy (CAR T‑cell therapy). Leukapheresis is used to remove T‑lymphocytes from the leukocytes, and CARs are created through genetic engineering. Without the aid of a major histocompatibility complex, these genetically modified receptors lyse malignant tissues by interacting directly with the carcinogen. Additionally, the outcomes of preclinical and clinical studies reveal that CAR T‑cell therapy has proven to be a potential therapeutic contender against metastatic breast cancer (BCa), triple‑negative, and HER 2+ve BCa. Nevertheless, unique toxicities, including (cytokine release syndrome, on/off‑target tumour recognition, neurotoxicities, anaphylaxis, antigen escape in BCa, and the immunosuppressive tumour microenvironment in solid tumours, negatively impact the mechanism of action of these receptors. In this review, the potential of CAR T‑cell immunotherapy and its method of destroying tumour cells is explored using data from preclinical and clinical trials, as well as providing an update on the approaches used to reduce toxicities, which may improve or broaden the effectiveness of the therapies used in BCa.
癌症是全球死亡率上升的主要原因之一,也是最显著的原因之一,每年导致近 1000 万人死亡。已经设计出特定的方法来治疗癌性肿瘤。必须在细胞和遗传水平上开发有效的治疗方法。免疫疗法通过为难治性恶性肿瘤患者提供持续缓解,提供了有希望的结果。由于最近的临床试验结果,基因修饰的 T 淋巴细胞已成为治疗实体瘤、血液恶性肿瘤和复发/难治性 B 淋巴细胞恶性肿瘤的新治疗方法;该治疗方法被称为嵌合抗原受体 T 细胞疗法(CAR T 细胞疗法)。白细胞分离术用于从白细胞中去除 T 淋巴细胞,并且通过基因工程创建 CAR。这些经过基因修饰的受体无需主要组织相容性复合物的帮助,通过与致癌剂直接相互作用裂解恶性组织。此外,临床前和临床研究的结果表明,CAR T 细胞疗法已被证明是一种针对转移性乳腺癌(BCa)、三阴性和 HER2+BCa 的潜在治疗候选药物。然而,独特的毒性,包括(细胞因子释放综合征、脱靶肿瘤识别、神经毒性、过敏反应、BCa 中的抗原逃逸和实体瘤中的免疫抑制肿瘤微环境,会对这些受体的作用机制产生负面影响。在这篇综述中,使用临床前和临床试验的数据探讨了 CAR T 细胞免疫疗法的潜力及其破坏肿瘤细胞的方法,并提供了有关减轻毒性的方法的最新信息,这可能会提高或扩大 BCa 中使用的治疗方法的有效性。