Fig. 6: Anti-pTα ADCs impair cell cycle progression and cell proliferation of pre-TCR+ T-ALL cells.
From: Pre-TCR-targeted immunotherapy for T cell acute lymphoblastic leukemia
a, Illustration of the modular nature of anti-pTα-DM1 and anti-pTα-MMAE ADCs, showing non-cleavable (MCC) and cleavable (SC-VC-PABC) linkers used. b, Representative cell cycle profiles of SupT1 pre-TCR+ cells left untreated (medium) or treated with drug-free anti-pTα monoclonal antibody, anti-pTα-DM1 or anti-pTα-MMAE ADCs, or their respective isotype-matched controls for 4 days. Numbers indicate percentages of cells in the G2 and M phases of the cell cycle. c, Mean percentages ± s.e.m. of cells in the G2 and M phases of the cell cycle within the indicated pre-TCR-positive (SupT1, JR.pTα) and pre-TCR-negative (CUTLL1, HPB-ALL, JR.MigR1) cell lines, treated as in b. In the left bar plots, for SupT1 cells untreated and anti-pTα-DM1-treated, n = 8 each; IgG2a-DM1-treated, n = 6; and anti-pTα-treated, n = 7 (****P < 0.0001). For CUTLL1 cells untreated, n = 7; IgG2a-DM1-treated, n = 4; and anti-pTα- and anti-pTα-DM1-treated, n = 3 each. For HPB-ALL untreated, n = 7; IgG2a-DM1-treated, n = 4, and anti-pTα- and anti-pTα-DM1-treated, n = 3 each. In the right bar plots, n = 6 for each group of SupT1, JR.MigR1 and JR.pTα cells. d, Relative cell proliferation of the indicated leukemic cell lines recovered after in vitro treatment as in b. Data are shown as the mean ± s.e.m. percentages of recovered treated cells relative to untreated cells. In the right bar plots, for SupT1 cells untreated, n = 4; IgG2a-DM1-treated, n = 7; and anti-pTα- and anti-pTα-DM1-treated, n = 8 each (****P < 0.0001). For CUTLL1 and HPB-ALL cells untreated, n = 7 each; IgG2a-DM1- and anti-pTα-DM1-treated, n = 3 each; and anti-pTα-treated, n = 4 each (*P = 0.0213, ****P < 0.0001). Data were analyzed by two-way-ANOVA with a Tukey’s multiple-comparisons test.
