CytomX Therapeutics, a biopharmaceutical company developing investigational Probody™ therapeutics for the treatment of cancer, and The University of Texas MD Anderson Cancer Center have agreed to jointly research Probody-enabled chimeric antigen receptor natural killer (CAR-NK) cell therapies, to be known as ProCAR-NK cell therapies (Probody-enabled CAR-NK Cell).

NK cells are cytotoxic lymphocytes that comprise a central component of the innate immune system. When these cells are engineered to express CARs that target proteins found on cancer cells, they demonstrate powerful anti-tumor responses. The resulting therapeutic class has potential advantages over CAR-T cells, including simpler manufacturing.

Based on the agreement, researchers at MD Anderson will leverage their expertise in developing allogeneic umbilical cord blood and peripheral blood derived NK-cell therapies and combine it with CytomX’s Probody technology to address new targets for this novel modality in cancer immunotherapy. Designed for more precise binding to tumors and reduced binding to healthy tissue, ProCAR-NK cell therapies will be created against targets for which safety and toxicity have traditionally been limiting factors for CAR cell therapies.

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Multiple targets
CytomX and MD Anderson will combine efforts in the development of ProCAR-NK cell therapies against multiple targets.  As part of the agreement, CytomX will have the option to license therapeutics that demonstrate preclinical proof of concept for clinical and commercial development.

“Our researchers see distinct promise in NK cells, as their role in the innate immune system enables immediate tumor killing effect compared to T-cells. In addition, CAR-NK cells have the opportunity to be off the shelf therapies as opposed to autologous CAR-T cell therapies,” said Katy Rezvani, M.D., Ph.D., professor, department of Stem Cell Transplantation and Cellular Therapy who has conducted more than a decade of research in NK-cell therapies. “By combining these advantages of CAR-NK cell therapies with the added targeting of this novel technology, we believe that we can create therapies that realize the full potential of the therapeutic class,” she continued.  Rezvani will be collaboratng with  MD Andersn’s Elizabeth Shpall, M.D., professor, department of Stem Cell Transplantation and Cellular Therapy.

Selective binding
Therapeutics developed with CytomX’s Probody platform have a mask linked to the antibody’s antigen-binding site designed to avoid the binding of antigens on healthy tissue. The mask is cleaved by proteases found in the tumor microenvironment, allowing Probody therapeutic to selectively bind to tumor cells. This binding selectivity allows CytomX to potentially expand the therapeutic window for both existing and new antigen targets. CytomX’s pipeline of wholly owned and partnered programs includes development-stage Probody cancer immunotherapies, Probody drug conjugates and Probody bispecifics.

“The progress we continue to make within our pipeline has shown that Probody therapies offer important advantages over traditional antibodies, with the potential for creating safe and effective cancer immunotherapies and antibody-drug conjugates,” noted Sean McCarthy, D.Phil., chief executive officer of CytomX. “This collaboration will allow us to draw on world-class research from MD Anderson in the field of CAR-NK cell therapies and extend our platform to this exciting modality.”

“Our Probody technology leverages dysregulated protease activity found in the tumor microenvironment,” McCarthy explained. “A Probody therapeutic is engineered in such a way that its target binding region is masked. This limits binding to the target on healthy tissue. However, when Probody therapeutics encounter proteases near tumor tissue, the proteases remove the mask from the Probody therapeutic. The activated Probody therapeutic can then bind to its target on the tumor, localizing the efficacy of a potent antibody-based therapeutic.”

“In healthy tissue, where protease activity is regulated and minimal, our preclinical data suggests that the target-binding region of the Probody therapeutic remains masked and unable to bind,” McCarthy concludes.


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