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

News, Oncotarget

January 17, 2023
Research Article

“Taken together, these findings provide a strong rationale for potently and selectively targeting of CD74 in patients with B-NHL [B-cell non-Hodgkin lymphoma].” 

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BUFFALO, NY- January 17, 2023 – A new research paper was published in Oncotarget’s Volume 14 on January 12, 2023, entitled, “Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001.”

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. 

In this new study, researchers 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 from Sutro Biopharma reported the results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL. 

“In order to explore the potential of STRO-001 in NHL, in the present study we investigated CD74 expression in cell types found in bone marrow, evaluated its cytotoxicity in NHL cell lines, and assessed its antitumor efficacy and toxicity in xenograft models of 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.”

DOI: https://doi.org/10.18632/oncotarget.28341

Correspondence to: Xiaofan Li & Arturo Molina 

Emails: xli@sutrobio.com & amolina@sutrobio.com 

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Keywords: CD74, antibody-drug conjugate, non-Hodgkin lymphoma, xenograft models, STRO-001

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