Niaz Muhammad O, Sun Michael, Ramirez-Fort Marigdalia K, Niaz Muhammad J
Internal Medicine, Sharif Medical City Hospital, Lahore, PAK.
Internal Medicine, Weill Cornell Medicine, New York, USA.
Cureus. 2020 Feb 29;12(2):e7147. doi: 10.7759/cureus.7147.
Cancer cells can be selectively targeted by identifying and developing antibodies to specific antigens present on the cancer cell surface. Cytotoxic agents can be conjugated to these antibodies that bind to these cell surface antigens in order to significantly increase the therapeutic index of whichever cytotoxic agent is utilized. This approach of conjugating the cytotoxic drugs to antibodies to target specific surface antigens enhances the anti-tumor activity of antibodies and improves the tumor-to-normal tissue selectivity of chemotherapy. Critical parameters in the development of these antibody-drug conjugates include: 1) selection of most appropriate antigen, 2) the ability of an antibody to be internalized after binding to the antigen, 3) cytotoxic drug potency and 4) stability of the antibody-drug conjugate. For prostate cancer, prostate-specific membrane antigen (PSMA, also known as folate hydrolase-1) is the most validated theragnostic target to date. PSMA is overexpressed on the prostate cancer cell surface, which makes it an even better target for selective drug delivery through conjugated antibodies. Here, we review the PSMA-based antibody-drug conjugates for metastatic castration-resistance prostate cancer (mCRPC).
通过识别和开发针对癌细胞表面特定抗原的抗体，可以选择性地靶向癌细胞。细胞毒性药物可以与这些与细胞表面抗原结合的抗体偶联，从而显著提高所使用的任何细胞毒性药物的治疗指数。将细胞毒性药物与抗体偶联以靶向特定表面抗原的这种方法增强了抗体的抗肿瘤活性，并提高了化疗对肿瘤组织与正常组织的选择性。开发这些抗体-药物偶联物的关键参数包括：1）选择最合适的抗原；2）抗体与抗原结合后被内化的能力；3）细胞毒性药物的效力；4）抗体-药物偶联物的稳定性。对于前列腺癌，前列腺特异性膜抗原（PSMA，也称为叶酸水解酶-1）是迄今为止最有效的诊疗靶点。PSMA在前列腺癌细胞表面过度表达，这使其成为通过偶联抗体进行选择性药物递送的更佳靶点。在此，我们综述了用于转移性去势抵抗性前列腺癌（mCRPC）的基于PSMA的抗体-药物偶联物。
