12:00 AM
Nov 12, 2015
 |  BC Innovations  |  Product R&D

Probodies, anticancer

How CytomX's Probodies improve safety across immuno-oncology modalities

How successful checkpoint inhibitors and chimeric antigen receptor (CAR) T cells will be at revolutionizing oncology hangs largely on whether it will be possible to curb their on-target but off-tissue toxicities. CytomX Therapeutics Inc. is using its Probody platform to restrict activity to tumors by capitalizing on enzymes unique to the tumor microenvironment. The company believes that by improving safety, its technology can expand the range of targets, indications and therapeutic combinations possible in cancer immunotherapy.

Over the past eight weeks, CytomX has presented the first data on its Probody platform for three different types of cancer immunotherapies - checkpoint inhibitors, antibody-drug conjugates (ADCs) and T cell-engaging bispecific antibodies (TCBs) - and announced a new partnership on a fourth, CAR-NK cells.

"Probodies are designed to bind tumors to protect healthy tissue. The rationale is that antibody therapeutics, particularly the recent wave of highly potent oncology modalities, come with significant side effects that can limit utility," said CytomX CEO Sean McCarthy.

At the September meeting of the American Association for Cancer Research (AACR), Cancer Research Institute (CRI), Association for Cancer Immunotherapy (CIMT) and European Academy of Tumor Immunology (EATI), CytomX presented preclinical data showing its lead candidate CX-072, an anti-PD-L1 probody, decreased tumor growth as effectively as standard antibodies, but without the autoimmune toxicities.

Earlier this week, CytomX presented additional preclinical data at the AACR-National Cancer Institute (NCI)-European Organization for Research and Treatment of Cancer (EORTC) meeting in Boston, showing its Probody platform can improve the safety of two other types of cancer immunotherapies: ADCs and TCBs.

And on November 5th, the company announced a research collaboration with the University of Texas MD Anderson Cancer Center to apply the Probody technology to CAR-NK cells. Like CAR T cells, CAR-NK cells are engineered ex vivo to express antigen-binding receptors that direct the cells to tumor antigens.

The Probody platform involves modifying therapeutic antibodies with an N-terminal, cleavable chemical mask that blocks activity. The molecules contain an antibody and a chemical mask at the antibody-binding site, linked by a substrate specific for proteases in the tumor microenvironment. The design prevents the agents from binding antigens in circulation, but allows them to be activated upon exposure to the proteases, which cleave the linker and release the chemical mask. (See Figure: CytomX's Probodies)

Although CytomX originally developed the technology to produce antibodies against a range of tumor antigens, about three years ago it switched gears to looking at safety problems of antibody-based therapies with a specific focus on immuno-oncology.

"Around 2011 and 2012, the field of cancer immunotherapy...

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