Fig. 1
From: Sialyl-Tn serves as a potential therapeutic target for ovarian cancer
Demonstrating on-target effects and response of humanized anti-STn-ADC in pre-clinical models. SKOV3CTL cells which express little to no STn and SKOV3 cells that were stably transfected with ST6GalNac1 to express elevated levels of STn (SKOV3-ST6GALNAC1) were plated in 96-well plate and then treated the next day with 0, 2.5, 5, 10, 50 or 100 nM of humanized anti-STn ADC (A, B). Seventy-two hours later the metabolic activity as an indirect measure of viability was assessed via MTT assay. The humanized anti-STn-ADC did not affect the SKOV3CTL cells, whereas a dose-dependent decrease in metabolic activity was evident in the SKOV3 cells with elevated levels of STn. Figure 1C, D show the response of 2 independent HGSOC PDX models expressing different levels of STn. Following randomization of mice in each of the arms (n = minimum of 4 mice/arm), they were treated with either vehicle, an isotype-ADC, or anti-STn-ADC weekly at a dose of 5 mg/kg. The graph showing the collective results in mice harboring tumors with high percentage STn positive tumor cells are shown in panel C and those hosting tumor with low a percentage of STn positive tumor cells are shown in panel D. Panel E represents a schematic of the sequential and combination treatment strategy. Panel F represents the results of the multi-arm experiment included one arm receiving vehicle at days 0, 7, 14 and 21 (Black Line); one arm received anti-STn-ADC at day 0, 7, 14 and 21 (Red Line); one arm received the combination of anti-STn-ADC and carboplatin/paclitaxel (on days 0, and 7) which was then followed by weekly PBS (on days 14, 21 Blue Line). One arm beginning with a larger number of mice hosting tumor received carboplatin and paclitaxel (1 x weekly x 2 weeks, days 0, and 7) after which the mice were then randomized across two additional arms. One receiving just PBS on days 14 and 21 (Orange Line) after cessation of carboplatin/paclitaxel (which results in a resurgence of tumor growth). The final sub arm received anti-STn -ADC (on days 14 and 21) following the cessation of the carboplatin/paclitaxel (Green Line) to assess whether it could impede the resurgence. At the end of the experiment all arms had a minimum of 4 mice. Asterisks represent differences (p < 0.05) compared to vehicle controls