Scientific publications

Publications by CytomX scientists and articles related to protease biology
and the Probody platform.

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Probody checkpoint inhibitors

PD-L1 (PROCLAIM CX-072)

PROCLAIM-CX-072: Monotherapy for Advanced Triple-Negative Breast Cancer With Skin Metastases in a Phase 1/2a Trial of the PD-L1 Probody Therapeutic CX-072

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Sylvia Adams, Erika Hamilton, Patrick A. Ott, Daniel Cho, Kevin Kalinsky, Patricia LoRusso, Matthias Will, Vanessa Huels, Beverly Benson, Carmen Murias, Hendrik-Tobias Arkenau. Poster presented at the 41st Annual San Antonio Breast Cancer Symposium, San Antonio, Texas.

Preliminary Evidence of Intratumoral Activation and Immunomodulatory Effect of CX-072, a Probody Therapeutic Antibody Prodrug Targeting PD-L1, in a Phase 1/2 Trial

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Susan K. Lyman, Judi Gordon, Amy DuPage, Preeti Pramanik, Bruce Howng, Ivan A. Zein, Michael B. Winter, Irina K. Popova, Olga Vasiljeva, James Jones, Ken Wong, Victoria Singson, Jennifer Richardson, Beiyao Zheng, Mark Stroh, Lori Carman, Vanessa Huels, Karen Autio, Valentina Boni, Daniel Cho, Javier Garcia-Corbacho, Iván Victoria Ruiz, Omid Hamid, Nataliya Uboha, Elisabeth de Vries, Anthony El-Khoueiry, Alexander Spira, Rachel E. Sanborn, Fiona Thistlethwaite, Hendrik-Tobias Arkenau, Johanna Bendell, Patrick A. Ott, Naiyer Rizvi, Matthias Will, W. Michael Kavanaugh, Aung Naing, Luc R. Desnoyers. Poster presented at SITC 2018, November 7-11, Washington, D.C.

Preliminary Results of PROCLAIM-CX-072: The First-in-Human, Dose-Finding Trial of PD-L1 Probody Therapeutic CX-072 as Monotherapy in Patients With Advanced Solid Tumors

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Valentina Boni, Javier Garcia-Corbacho, Patrick A. Ott, Daniel Cho, Karen A. Autio, Nataliya Uboha, Alexander I. Spira, Rachel Humphrey, Matthias Will, Aung Naing, Fiona Thistlethwaite, Elisabeth de Vries, Hendrik-Tobias Arkenau. Poster presented at ESMO 2018, October 19-23, Munich, Germany.

Preliminary Results of the First-in-Human, Dose-Finding PROCLAIM-CX-072 Trial Evaluating the PD-L1 Probody Therapeutic CX-072 in Combination With Ipilimumab in Patients With Advanced Solid Tumors

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Ruth Plummer, Rachel E. Sanborn, Elisabeth de Vries, Patricia LoRusso,Hendrik-Tobias Arkenau, Nataliya Uboha, Jerzy Wydmanski, Mary Josephine Fidler, Valentina Boni, Javier Garcia-Corbacho, Rachel Humphrey, Matthias Will, Karen A. Autio, Anthony El-Khoueiry, C. Willemien Menke-van der Houven van Oordt, Fiona Thistlethwaite. Poster presented at ESMO 2018, October 19-23, Munich, Germany.

Preliminary Interim Results of the First-in-Human, Dose-Finding PROCLAIM-CX-072 Trial of the PD-L1 Probody Therapeutic (Pb-Tx) CX-072 in Combination with Ipilimumab (ipi) in Patients (pts) with Advanced Solid Tumors

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Rachel E. Sanborn, Catharina Wilhelmina Menke, Karen A. Autio, Hendrik-Tobias Arkenau, Javier Garcia Corbacho, Patricia LoRusso, Elizabeth Ruth Plummer, Nataliya Volodymyrivna Uboha, Morganna Louise Freeman, Jerzy Wydmanski, Vanessa Huels, Beiyao Zheng, Matthias Will, Rachel W. Humphrey, Fiona Thistlethwaite, Elisabeth G.E. de Vries, Anthony B. El-Khoueiry. Poster presented at ASCO 2018, June 1-5, Chicago, Illinois.

Preliminary Results of the First-in-Human, Dose-Finding PROCLAIM-CX-072 Trial of the PD-L1 Probody Therapeutic CX-072 as Monotherapy in Patients (pts) with Advanced Solid Tumors

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Karen A. Autio, Hendrik-Tobias Arkenau, Bert H. O’Neil, Johanna C. Bendell, Anthony El-Khoueiry, James Strauss, Amy Weise, Nataliya Volodymyrivna Uboha, Naiyer A. Rizvi, Beiyao Zheng, Luc Desnoyers, Mark Stroh, Lori Carman, Rachel W. Humphrey, Matthias Will, Valentina Boni, Alexander I. Spira, Aung Naing. Poster presented at ASCO 2018, June 1-5, Chicago, Illinois.

A PD-L1-targeted Probody™ Therapeutic Provides Anti-Tumor Efficacy While Minimizing Induction of Systemic Autoimmunity in Preclinical Studies

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Chihunt Wong, Li Mei, Kenneth R. Wong, Jennifer Razo, Chanty Chan, Elizabeth Menendez, Shouchun Liu, Olga Vasiljeva, Jennifer H. Richardson, James W. West, W. Michael Kavanaugh, Bryan A. Irving. Poster presented at CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference 2015, September 16-19, New York, New York.

PROCLAIM-CX-072: A First-in-Human Trial to Assess Tolerability of the Protease-Activatable Anti–PD-L1 Probody™ CX-072 in Solid Tumors and Lymphomas

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Alexander I. Spira, Mark R. Middleton, Aung Naing, Karen A. Autio, John J. Nemunaitis, Johanna C. Bendell, Michael Gordon, Rachel W. Humphrey, Chihunt Wong, Naiyer A. Rizvi. Poster presented at ASCO 2017, June 2-6, Chicago, Illinois.

The First-in-Human, Dose-Finding PROCLAIM-CX-072 Trial to Assess the Antitumor Activity and Tolerability of the Probody™ Therapeutic CX-072 as Monotherapy and in Combination With Ipilimumab or Vemurafenib in Solid Advanced Tumors and Lymphomas

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Valentina Boni, Javier Garcia-Corbacho, Jaime Feliu, Jerzy Wydmanski, Zsolt Horvath, Igor Bondarenko, Bryan Irving, Matthias Will, Elisabeth de Vries, Fiona Thistlethwaite. Poster presented at ESMO 2017, September 8-12, Madrid, Spain.

PD-1 (CX-188)

PD-1 Probody™ Therapeutic Anti-tumor Efficacy and Protection Against Autoimmunity in Preclinical Models

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Kimberly A. Tipton, Chanty Chan, Kenneth R. Wong, Victoria Singson, Laura P. Serwer, Yuanhui Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, Bryan A. Irving and James W. West. Poster presented at AACR 2016, April 16-20, New Orleans, Louisiana.

CTLA-4

Probody™ Therapeutic Targeting PD-1 Provides Preclinical Anti-tumor Efficacy While Minimizing Induction of Autoimmunity as a Single Agent and in Combination with CTLA-4 Blockade

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Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhui Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James W. West and Bryan A. Irving. Poster presented at SITC 2016, November 9-13, National Harbor, Maryland.

Probody drug conjugates

CD166 (CX-2009)

Development of a Probody™ Drug Conjugate (PDC) Targeting CD166 for the Treatment of Multiple Cancers

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Annie Yang Weaver, Shweta Singh, Amy DuPage, Jason Sagert, Jeanne Flandez, Elizabeth Menendez, Judi Ford, Michael Krimm, Stephen Moore, Margaret Nguyen, Andrew Jang, Eric Brecht, Yuanhui Huang, Linnea Diep, Nicole Lapuyade, Tereza Sputova, James West, Olga Vasiljeva, Shouchun Liu, Jennifer Richardson, W. Michael Kavanaugh, Jonathan A. Terrett, Luc R. Desnoyers. Poster presented at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2015, November 5-9, Boston, Massachusetts.

PROCLAIM-CX-2009: A First-in-Human Trial to Evaluate CX-2009 in Adults With Metastatic or Locally Advanced Unresectable Solid Tumors

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Javier Garcia-Corbacho, Alexander Spira, Valentina Boni, Jaime Feliu, Mark Middleton, Howard Burris, Annie Yang Weaver, Matthias Will, James Harding, Funda Meric-Bernstam, Volker Heinemann. Poster presented at ESMO 2017, September 8-12, Madrid, Spain.

CD71 (CX-2029)

Preclinical Development of a Probody™ Drug Conjugate (PDC) Targeting CD71 for the Treatment of Multiple Cancers

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Shweta Singh, Amy DuPage, Annie Yang Weaver, Michael Krimm, Clayton White, Jason Sagert ,Yuanhui Huang, Linnea Diep, Shouchun Liu, Jennifer Richardson, W. Michael Kavanaugh, Jonathan A. Terrett, Luc R. Desnoyers. Poster presented at AACR 2016, April 16-20, New Orleans, Louisiana.

Developing a CD71-Targeting Probody™ Drug Conjugate (PDC) for Activity in Multiple Solid Tumor and Lymphoma Models and for Tolerability in Non-human Primates

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Shweta Singh, Laura Serwer, Niharika Chauhan, Amy DuPage, Michael Krimm, Ken Wong, Yuanhui Huang, Andrew Jang, Eric Ureno, Adam Miller, Sarah Patrick, Shanti Duvur, Fritz Buchanan, Matthew Ravn, Rob Leanna, Ilaria Badagnani, Tracy Henriques, Shouchun Liu, Luc Desnoyers, Claus Krebber, Sridhar Viswanathan, Jennifer Richardson, Susan Morgan-Lappe and W. Michael Kavanaugh. Poster presented at AACR-NCI-EORTC International Conference on Molecular Targets 2017, October 26-30, Philadelphia, Pennsylvania.

A Multi-Analyte HPLC-MS/MS Approach to Assessing Exposure of a Probody™ Drug Conjugate in Preclinical Studies

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Laura P. Serwer, Shweta Singh, Claus Krebber, Shouchun Liu, Niharika Chauhan, Robert Leanna, Hong Lu, Ilaria Badagnani, Tracy Henriques, Susan Morgan-Lappe, William Mylott Jr., Sridhar Viswanathan, Jennifer H. Richardson, W. Michael Kavanaugh. Poster presented at AACR-NCI-EORTC International Conference on Molecular Targets 2017, October 26-30, Philadelphia, Pennsylvania.

Probody T cell bispecifics

EGFR-CD3

EGFR-CD3 Bispecific Probody™ Therapeutic Induces Tumor Regressions and Increases Maximum Tolerated Dose > 60 fold in Preclinical Studies

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Leila M. Boustany, Sherry L. La Porte, Laurie Wong, Clayton W. White, Linnea Diep, Yuanhui Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, Bryan A. Irving. Poster presented at AACR-NCI-EORTC International Conference on Molecular Targets 2017, October 26-30, Philadelphia, Pennsylvania.

Platform

Platform Child

Targeting Drug Conjugates to the Tumor Microenvironment: Probody Drug Conjugates

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Lin J., Sagert J. (2018) Targeting Drug Conjugates to the Tumor Microenvironment: Probody Drug Conjugates. In: Damelin M. (ed). Innovations for Next-Generation Antibody-Drug Conjugates. Cancer Drug Discovery and Development. Humana Press, Cham.

In vivo imaging of protease activity by Probody therapeutic activation

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Biochimie; Vasiljeva O, et al; November 2015.

Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index

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Science Translational Medicine; Desnoyers, L., Vasiljeva, O., Richardson, J., Yang, A., Menendez, E., Liang, T.,… Lowman, H.; October 2013

Imaging a functional tumorigenic biomarker in the transformed epithelium

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Proceedings of the National Academy of Sciences USA; LeBeau, A. et al; January 2013

Identification of protease exosite-interacting peptides that enhance substrate cleavage kinetics

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Biological Chemistry; Jabaiah A, et al; September 2012.

Site-specific targeting of antibody activity in vivo mediated by disease-associated proteases

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Journal of Controlled Release; Erster, O. et al; August 2012

Emerging principles in protease-based drug discovery

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Nature Reviews Drug Discovery; Drag, M. et al; September 2010

Evolutionary optimization of peptide substrates for proteases that exhibit rapid hydrolysis kinetics

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Biotechnology and Bioengineering; Boulware K, et al; June 2010.

Tumor detection by imaging proteolytic activity

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Cancer Research; Darragh M, et al; February 2010.

Methods for the proteomic identification of protease substrates

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Current Opinion in Chemical Biology; Agard N, et al; December 2009.

The urokinase plasminogen activator system: a target for anti-cancer therapy

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Current Cancer Drug Targets; Ulisse S, et al; February 2009.

Matrix metalloproteases: underutilized targets for drug discovery

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Journal of Drug Targeting; Vartak D, et al; January 2007.

Matriptase and its putative role in cancer

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Cellular and Molecular Life Sciences; Uhland K, et al; December 2006.

Protease specificity determination by using cellular libraries of peptide substrates (CLiPS)

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Proceedings of the National Academy of Sciences USA; Boulware K, et al; May 2006.

Bacterial display using circularly permuted outer membrane protein OmpX yields high affinity peptide ligands

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Protein Science; Rice J, et al; April 2006.

Proteases, extracellular matrix, and cancer: a workshop of the path B study section

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American Journal of Pathology; DeClerck Y, et al; April 2004.