Department of Food Biotechnology, Medical University of Bialystok, Szpitalna 37 Street, 15-295 Bialystok, Poland.
Department of Gynaecology and Obstetrics, Medical University of Bialystok, M. Sklodowskiej-Curie 24A Street, 15-089 Bialystok, Poland.
Int J Mol Sci. 2021 Mar 28;22(7):3495. doi: 10.3390/ijms22073495.
Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome ( and mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.
近年来，我们对肿瘤生物学的认识不断提高，这导致了靶向分子疗法的发展，例如血管内皮生长因子 A（VEGF-A）拮抗剂、遗传性乳腺癌和卵巢癌综合征中的聚[ADP-核糖]聚合酶 1（PARP1）抑制剂（ 和 突变体），提高了生存率并改善了生活质量。然而，大多数卵巢癌（OC）患者仍然无法获得能够控制其疾病的靶向分子疗法，尤其是耐药或复发的患者。嵌合抗原受体（CARs）是位于 T 淋巴细胞或其他免疫细胞上的重组受体构建体，可改变其特异性和功能。因此，在寻找使用 CARs 进行成功的实体瘤治疗时，识别特定的细胞表面抗原至关重要。大量的体外和体内研究以及人类研究证明，靶向过度表达的分子，如粘蛋白 16（MUC16）、膜联蛋白 2（ANXA2）、受体酪氨酸蛋白激酶 erbB-2（HER2/neu），会导致高肿瘤细胞毒性和肿瘤负担减少。CARs 耐受性良好，副作用极小，并且可以抑制疾病进展。然而，由于 OC 在本质上具有高度的突变多样性和不同受体的过度表达，因此需要考虑针对这种癌症的个体化治疗方法。在本出版物中，我们想介绍涉及 CAR T 细胞治疗 OC 肿瘤的历史和现状，提出潜在的 T 细胞内在反应和耐药性决定因素，并介绍影响这种方法成功的外在因素。
