Fig. 7: Treatment of human T-ALL with pre-TCR targeting ADCs impairs tumor progression and increases overall survival in a preclinical in vivo assay.

a, Timeline of in vivo pre-TCR targeting immunotherapy based on administration of anti-pTα-MMAE or its corresponding isotype-matched control to NSG mice i.v. injected with T-ALL42 human cells (2 × 10⁶ cells per mouse) recovered from spleen xenografts of NSG mice. b, Mean ± s.e.m. percentages of T-ALL42 cells recovered at the indicated days from the peripheral blood of NSG mice (n = 6) treated as indicated in a; ****P < 0.0001. c, Kaplan–Meier survival curves of NSG mice in b were compared using a log-rank Mantel–Cox test, ****P < 0.0001. d, Timeline of in vivo pre-TCR targeting immunotherapy based on administration of drug-free anti-pTα monoclonal antibody, anti-pTα-DM1 or anti-pTα-MMAE ADCs, or their respective isotype-matched controls, or VxL chemotherapy, to SCID mice i.v. injected with T-ALL3 human cells (10⁶ cells per mouse) recovered from spleen xenografts of NSG mice. Doses of anti-pTα-DM1 and anti-pTα-MMAE ADCs were based on the drug-to-antibody ratio (DAR), which was three and six molecules of DM1 and MMAE per antibody molecule, respectively. e, Mean ± s.e.m. percentages of T-ALL3 cells recovered at the indicated days from the peripheral blood of SCID mice treated as indicated in d. For VxL treatment, n = 6; for IgG2a and anti-pTα treatment, n = 7 each; for IgG2a-DM1, IgG2a-MMAE, anti-pTα-DM1 and anti-pTα-MMAE, n = 6 each, from one experiment. f, Mean ± s.e.m. percentages of electronically gated CD3^loTCRαβ^neg cells infiltrating the peripheral blood of SCID mice in e at day 91 after transplant. For IgG2a and anti-pTα treatment, n = 7 each; for IgG2a-DM1, IgG2a-MMAE and anti-pTα-DM1 treatment, n = 6 each, and for anti-pTα-MMAE treatment, n = 4. Data were analyzed by a mixed-effects model (REML; b) or by one-way (f) or two-way (e) ANOVA with Tukey’s multiple-comparisons test. ***P = 0.0001; ****P < 0.0001.

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