Activated platelets in the tumor microenvironment for targeting of antibody-drug conjugates to tumors and metastases

ML Yap; JD McFadyen; X Wang; M Ziegler; YC Chen; A Willcox; CJ Nowell; AM Scott; EK Sloan; MP Hogarth; GA Pietersz; K Peter

Journal article

Activated platelets in the tumor microenvironment for targeting of antibody-drug conjugates to tumors and metastases

ML Yap, JD McFadyen, X Wang, M Ziegler, YC Chen, A Willcox, CJ Nowell, AM Scott, EK Sloan, MP Hogarth, GA Pietersz, K Peter

Theranostics | IVYSPRING INT PUBL | Published : 2019

DOI: 10.7150/THNO.29146

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Abstract

Rationale: Platelets are increasingly recognized as mediators of tumor growth and metastasis. Hypothesizing that activated platelets in the tumor microenvironment provide a targeting epitope for tumor-directed chemotherapy, we developed an antibody-drug conjugate (ADC), comprised of a single-chain antibody (scFv) against the platelet integrin GPIIb/IIIa (scFvGPIIb/IIIa) linked to the potent chemotherapeutic microtubule inhibitor, monomethyl auristatin E (MMAE). Methods: We developed an ADC comprised of three components: 1) A scFv which specifically binds to the high affinity, activated integrin GPIIb/IIIa on activated platelets. 2) A highly potent microtubule inhibitor, monomethyl auristatin..

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University of Melbourne Researchers

Xiaowei Wang Author

Andrew Scott Author

P. Mark Hogarth Author

Geoffrey Pietersz Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was funded by the National Health and Medical Research Council (NHMRC project grant: 1108670) of Australia and in part by the Victorian Government Operational Infrastructure Support Program. In addition, MLY is supported by the Research Training Program Scholarship, JDM is supported by the Sylvia and Charles Viertel Foundation Clinical Investigator Award, XW is supported by the National Heart Foundation of Future Leader Fellowship with the Paul Korner Innovation Award, YCC is supported by the National Heart Foundation Postdoctoral Fellowship, AMS is supported by a NHMRC Senior Practitioner Fellowship, EKS is supported by NHMRC 1147498. PMH is supported by the Rebecca Cooper Foundation and NHMRC project grants and KP is supported by a NHMRC Principal Research Fellowship.