Gatipotuzumab is a humanized monoclonal antibody that specifically targets the tumor-associated mucin-1 (TA-MUC1) epitope and has the potential to inhibit cancer progression[1]. DLL3 demonstrates high expression levels in small cell lung cancer (SCLC) and other neuroendocrine tumors, while showing minimal expression in normal tissues. This selective targeting mechanism enables Gatipotuzumab to deliver cytotoxic agents specifically to cancer cells expressing DLL3, thereby minimizing impact on healthy cells[2-3]. Further exploration is underway to investigate its potential utility in treating other DLL3-expressing neuroendocrine tumors[4].
Gatipotuzumab (0, 30, 60µg/mL) treatment of ovarian cancer cells (COV318, OV-90, OVCAR-3, SKOV-3) significantly reduced cell viability, as evidenced by decreased cell proliferation. Moreover, co-treatment of ovarian cancer cells with Gatipotuzumab (60µg/mL) and 4-hydroxy-tamoxifen (4-OHT, 5µM) further decreased cell viability at 48 and 72 hours, with a more pronounced effect than treatment with Gatipotuzumab or 4-OHT alone[5].
References:
[1] Ochsenreither S, Fiedler WM, Conte GD, et al. Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors. ESMO Open. 2022 Apr;7(2):100447.
[2] Owen DH, Giffin MJ, Bailis JM, et al. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019 Jun 18;12(1):61.
[3] Heublein S, Page S, Mayr D, et al. Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer. Int J Mol Sci. 2019 Jan 12;20(2):295.
[4] Heublein S, Friese K, Kost B, et al. TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer. J Cancer Res Clin Oncol. 2018 Oct;144(10):1899-1907.
[5] Heublein S, Page S, Mayr D, et al. Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer. Int J Mol Sci. 2019 Jan 12;20(2):295.
Gatipotuzumab是一种人源化单克隆抗体，特异性靶向Delta样配体3（DLL3）蛋白，可识别黏蛋白-1 的肿瘤特异性表位 (TA-MUC1)，具有潜在的抑制癌症发展的功能[1]。DLL3在小细胞肺癌（SCLC）和其他神经内分泌肿瘤中高表达，但在正常组织中表达极少。这种选择性靶向使Gatipotuzumab能够将细胞毒性药物特异性地传递给表达DLL3的癌细胞，从而减少对健康细胞的影响[2-3]。此外，Gatipotuzumab还在探索其在其他表达DLL3的神经内分泌肿瘤中的潜在应用[4]。
Gatipotuzumab（0、30、60µg/mL）处理卵巢癌细胞（COV318、OV-90、OVCAR-3、SKOV-3），显著降低了细胞的活性和增殖能力。此外，Gatipotuzumab（60µg/mL）与4-Hydroxytamoxifen（4-OHT，5µM）联合处理的卵巢癌细胞，在48小时和72小时后，细胞活性进一步降低，且这种降低效果比单独使用Gatipotuzumab或4-OHT更为显著[5]。