Cancer-oocyte SAS1B protein is expressed at the cell surface of multiple solid tumors and targeted with antibody-drug conjugates - Abstract

Sep 21, 2026

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SAS1B (sperm acrosomal SLLP1 binding protein) is present in oocytes and also reported in uterine and pancreatic cancers, where anti-SAS1B antibody-drug conjugates (ADCs) can arrest growth. This study characterizes SAS1B expression in cancers and normal tissues to test whether SAS1B is selectively displayed on tumor cell surfaces and can be therapeutically targeted. SAS1B levels and transcripts were assessed using immunohistochemistry, cDNA PCR, antibody mapping, immunofluorescence, and flow cytometry.

LanguageEnglish

CategoryResearch & Report

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Pages13

Reading Time33 min

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Open access Original research To cite: Mandal A, Shetty J, Tran CA, et al. Cancer-oocyte SAS1B protein is expressed at the cell surface of multiple solid tumors and targeted with antibody-drug conjugates. Journal for ImmunoTherapy of Cancer 2024;12:e008430 . doi:10.1136/jitc-2023-008430 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2023-008430](jitc-2023-008430)) . JCH died on Sep 17, 2016 CLSJ and JCH contributed equally. AM, JS and CAT are joint first authors. Accepted 26 February 2024 © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. For numbered affiliations see end of article. Correspondence to Dr Craig L Slingluff Jr; [cls8h@virginia.edu](cls8h@virginia.edu) Cancer-oocyte SAS1B protein is expressed at the cell surface of multiple solid tumors and targeted with antibody-drug conjugates Arabinda Mandal,1 Jagathpala Shetty,2 Christine A Tran ,1 Walter C Olson,1 Mriganka Mandal,3 Bhupal Ban,4,5 Eusebio S Pires,6,7 Sara J Adair ,1 Todd W Bauer,1 Craig L Slingluff Jr ,1 John C Herr5,7 ABSTRACT Background Sperm acrosomal SLLP1 binding (SAS1B) protein is found in oocytes, which is necessary for spermoocyte interaction, and also in uterine and pancreatic cancers. Anti-SAS1B antibody-drug conjugates (ADCs) arrested growth in these cancers. However, SAS1B expression in cancers and normal tissues has not been characterized. We hypothesized that SAS1B is expressed on the surface of other common solid cancer cells, but not on normal tissue cells, and might be selectively targeted therapeutically. Methods SAS1B expression in human normal and cancer tissues was determined by immunohistochemistry, and complementary DNA (cDNA) libraries were employed to PCR amplify human SAS1B and its transcripts. Monoclonal antibodies (mAbs) to human SAS1B were generated using mouse hybridomas. SAS1B deletion constructs were developed to map SAS1B’s epitope, enabling the creation of a blocking peptide. Indirect immunofluorescence (IIF) of human transfected normal and cancer cells was performed to assess SAS1B expression. SAS1B intracellular versus surface expression in normal and tumor tissues was evaluated by flow cytometry after staining with anti-SAS1B mAb, with specificity confirmed with the blocking peptide. Human cancer lines were treated with increasing mAb and ADC concentrations. ATP was quantitated as a measure of cell viability. Results SAS1B expression was identified in a subset of human cancers and the cytoplasm of pancreatic islet cells. Two new SAS1B splice variants were deduced. Monoclonal antibodies were generated to SAS1B splice variant A. Theepitope for mAbs SB2 and SB5 is between SAS1B amino acids 32–39. IIF demonstrated intracellular SAS1B expression in transfected kidney cells and on the cell surface of squamous cell lung carcinoma. Flow cytometry demonstrated intracellular SAS1B expression in all tumors and some normal cells. However, surface expression of SAS1B was identified only on cancer cells. SB2 ADC mediated dose-dependent cytotoxic killing of multiple human cancer lines. Conclusion SAS1B is a novel cancer-oocyte antigen with cell surface expression restricted to cancer cells. In vitro, it is an effective target for antibody-mediated cancer cell lysis. These findings support further exploration of SAS1B as a potential | WHAT IS ALREADY KNOWN ON THIS TOPIC | | --- | | ⇒ Sperm acrosomal SLLP1 binding protein (SAS1B) is a zinc metalloproteinase expressed in human oocytes that has also been shown to represent a potential immunotherapeutic target on human uterine cancers and pancreatic cancer cells. However, little is known about SAS1B expression on other solid organ malignancies. Interestingly, we later found that SAS1B is also expressed in normal human pancreatic islet cells, raising the concern for cross-reacti

FAQs

What question does this study address about SAS1B in cancer?

It tests whether SAS1B is expressed on the surface of other solid cancer cells while not being expressed on normal tissue cell surfaces, making it a selective therapeutic target.

How was SAS1B expression measured across tissues and cells?

SAS1B expression in human normal and cancer tissues was assessed by immunohistochemistry, transcript amplification by cDNA PCR, and surface versus intracellular expression by immunofluorescence and flow cytometry.

What did the study find about SAS1B localization in tumors versus normal tissues?

SAS1B expression was identified in a subset of cancers, with intracellular expression in tumors and some normal cells, but surface expression of SAS1B was restricted to cancer cells.

Sep 21, 2026

Uploaded by Finn