Oncotarget

Research Papers:

Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001

Xiaofan Li _, Cristina Abrahams, Abigail Yu, Millicent Embry, Robert Henningsen, Venita DeAlmeida, Shannon Matheny, Toni Kline, Alice Yam, Ryan Stafford, Trevor Hallam, Mark Lupher and Arturo Molina _

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Abstract

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

Correspondence to:

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

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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