Tebentafusp (IMCgp100) is a bispecific fusion protein to target gp100 peptide-HLA-A*02:01 (a melanoma-associated antigen). Tebentafusp guides T cells to kill gp100-expressing tumor cells via a high affinity T-cell receptor (TCR) binding domain and an anti-CD3 T-cell engaging domain. Tebentafusp leads to inflammatory cytokines and cytolytic proteins production, resulting in the direct lysis of tumour cells[1][2].
Tebentafusp 是一种识别由 HLA-A*0201 表达的黑色素瘤特异性蛋白 gp100 衍生的肽的ImmTAC[3]。
Tebentafusp (31 pM, 82 pM 和131 pM; 16 h) 刺激 PBMC 对 Mel526 细胞而不是 gp100 阴性 A375 细胞的细胞毒性脱颗粒活性[3]。
Tebentafusp (100 pM; 0-50h) 介导 CD8+ T 细胞 (虽然存在调节性 T 细胞) 的杀伤，表现在40-48小时内 caspase 3/7 的激活[3]。
Tebentafusp (100 pM; 0-80 h) 触发 CD4+ T 细胞亚群对黑素瘤细胞的细胞溶解[3]。
Tebentafusp (1, 12, 31, 82 和131 pM; 24 h 或 96 h) 增加颗粒酶 B 的含量，并诱导 CD4+ 和 CD8+ 细胞广泛释放细胞因子和趋化因子[3]。
Tebentafusp (10 μg/kg; 静脉注射) 在小鼠黑色素瘤模型中抑制肿瘤的生长[4]。
[1]. Middleton MR, et al. Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Clin Cancer Res. 2020 Nov 15;26(22):5869-5878.
[2]. Dhillon S. Tebentafusp: First Approval. Drugs. 2022 Apr;82(6):703-710.
[3]. Boudousquie C, et al. Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells. Immunology. 2017 Nov;152(3):425-438.
[4]. Baeuerle P A, et al. Passive immunotherapy by T cell-engaging bispecifi c antibodies[M]//Cancer Vaccines. CRC Press, 2015: 266-278.