Dubrovsky Leonid, Dao Tao, Gejman Ron S, Brea Elliott J, Chang Aaron Y, Oh Claire Y, Casey Emily, Pankov Dmitry, Scheinberg David A
Memorial Sloan Kettering Cancer Center ; New York, NY USA.
Oncoimmunology. 2015 Jun 1;5(1):e1049803. doi: 10.1080/2162402X.2015.1049803. eCollection 2016.
The major hurdle to the creation of cancer-specific monoclonal antibodies (mAb) exhibiting limited cross-reactivity with healthy human cells is the paucity of known tumor-specific or mutated protein epitopes expressed on the cancer cell surface. Mutated and overexpressed oncoproteins are typically cytoplasmic or nuclear. Cells can present peptides from these distinguishing proteins on their cell surface in the context of human leukocyte antigen (HLA). T cell receptor mimic (TCRm) mAb can be discovered that react specifically to these complexes, allowing for selective targeting of cancer cells. The state-of-the-art for TCRm and the challenges and opportunities are discussed. Several such TCRm are moving toward clinical trials now.
创建与健康人类细胞交叉反应有限的癌症特异性单克隆抗体(mAb)的主要障碍是癌细胞表面已知的肿瘤特异性或突变蛋白表位数量稀少。突变和过表达的癌蛋白通常位于细胞质或细胞核中。细胞可以在人类白细胞抗原(HLA)的背景下,将来自这些独特蛋白的肽呈递在其细胞表面。可以发现对这些复合物具有特异性反应的T细胞受体模拟物(TCRm)单克隆抗体,从而实现对癌细胞的选择性靶向。本文讨论了TCRm的最新进展以及面临的挑战和机遇。目前有几种这样的TCRm正走向临床试验。