Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001
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Xiaofan Li1, Cristina Abrahams1, Abigail Yu1, Millicent Embry1, Robert Henningsen1, Venita DeAlmeida1, Shannon Matheny2, Toni Kline1, Alice Yam1, Ryan Stafford1, Trevor Hallam1, Mark Lupher1 and Arturo Molina2
1 Research Development, Sutro Biopharma, South San Francisco, CA 94080, USA
2 Clinical Development, Sutro Biopharma, South San Francisco, CA 94080, USA
|Xiaofan Li,||email:||[email protected]|
|Arturo Molina,||email:||[email protected]|
Keywords: CD74; antibody-drug conjugate; non-Hodgkin lymphoma; xenograft models; STRO-001
Received: October 04, 2022 Accepted: October 27, 2022 Published: January 12, 2023
Overexpression of CD74, a type II transmembrane glycoprotein involved in MHC class II antigen presentation, has been reported in many B-cell non-Hodgkin lymphomas (NHLs) and in multiple myeloma (MM). STRO-001 is a site-specific, predominantly single-species antibody-drug conjugate (ADC) that targets CD74 and has demonstrated efficacy in xenograft models of MM and tolerability in non-human primates. Here we report results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL. STRO-001 displayed nanomolar and sub-nanomolar cytotoxicity in 88% (15/17) of cancer cell lines tested. STRO-001 showed potent cytotoxicity on proliferating B cells while limited cytotoxicity was observed on naïve human B cells. A linear dose-response relationship was demonstrated in vivo for DLBCL models SU-DHL-6 and U2932. Tumor regression was induced at doses less than 5 mg/kg, while maximal activity with complete cures were observed starting at 10 mg/kg. In MCL Mino and Jeko-1 xenografts, STRO-001 starting at 3 mg/kg significantly prolonged survival or induced tumor regression, respectively, leading to tumor eradication in both models. In summary, high CD74 expression levels in tumors, nanomolar cellular potency, and significant anti-tumor in DLBCL and MCL xenograft models support the ongoing clinical study of STRO-001 in patients with B-cell NHL.
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