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[1]Faroudi, Mustapha, et al. “Lytic versus stimulatory synapse in cytotoxic T lymphocyte/target cell interaction: manifestation of a dual activation threshold.” Proceedings of the National Academy of Sciences 100.24 (2003): 14145-14150.
[2]Riquelme, Erick, et al. “The duration of TCR/pMHC interactions regulates CTL effector function and tumor©\killing capacity.” European journal of immunology 39.8 (2009): 2259-2269.
[3]Malik-Chaudhry, Harbani K., et al. “TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL.” MAbs. Vol. 13. No. 1. Taylor & Francis, 2021.
[4]Staflin, Karin, et al. “Target arm affinities determine preclinical efficacy and safety of anti-HER2/CD3 bispecific antibody.” JCI insight 5.7 (2020).
[5]Zuch de Zafra, Christina L., et al. “Targeting multiple myeloma with AMG 424, a novel anti-CD38/CD3 bispecific T-cell¨Crecruiting antibody optimized for cytotoxicity and cytokine release.” Clinical Cancer Research 25.13 (2019): 3921-3933.
[6]Crawford, Alison, et al. “A Mucin 16 bispecific T cell¨Cengaging antibody for the treatment of ovarian cancer.” Science translational medicine 11.497 (2019): eaau7534.
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