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Updated: Dec 11, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma
Ruriko Nakae1, Shinya Matsuzaki2, Satoshi Serada3
1Department of Obstetrics and Gynecology, Osaka University, Osaka, Japan; Department of Obstetrics and Gynecology, Sumitomo Hospital, Osaka, Japan.
Background:
Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma.
Objective:
This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma.
Study Design:
Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models).
Results:
CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm3; relative reduction, 84.7%; P<.001).
Conclusion:
Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.
Insights
This study found that uterine leiomyosarcoma (LMS) highly expresses CD70. A CD70-antibody-drug conjugate demonstrated significant antitumor activity against LMS in preclinical models, suggesting a potential new targeted therapy for this rare cancer.
Area of Science:
- Gynecologic Oncology
- Cancer Biology
- Pharmacology
Background:
- Uterine leiomyosarcoma (LMS) is a rare, aggressive malignancy with limited treatment options.
- Recurrence is common even after complete surgical removal.
- Current therapies offer modest efficacy, highlighting the need for novel treatment strategies.
Purpose of the Study:
- To investigate the expression of CD70 in uterine LMS.
- To evaluate the therapeutic potential of a CD70-antibody-drug conjugate (ADC) against LMS.
Main Methods:
- Membrane protein expression profiling of LMS cell lines and normal myometrium.
- Validation of CD70 expression using Western blotting, flow cytometry, and immunohistochemistry.
- Development and in vitro/in vivo testing of a CD70-ADC in cell lines, xenograft, and patient-derived xenograft models.
Main Results:
- CD70 was identified as a specific antigen highly expressed in most uterine LMS samples (90.5%).
- The developed CD70-ADC exhibited potent and specific antitumor activity against CD70-positive LMS cells in vitro.
- Significant tumor growth inhibition was observed in vivo using both mouse xenograft and patient-derived xenograft models.
Conclusions:
- Uterine leiomyosarcoma exhibits high CD70 expression, making it a viable therapeutic target.
- CD70-targeted antibody-drug conjugate therapy shows significant promise as a novel treatment strategy for uterine LMS.
- Further clinical investigation of CD70-ADCs is warranted for patients with uterine leiomyosarcoma.
