Patients with kidney cancer are in dire need of effective treatment options as their cancer cells become resistant to nearly all conventional modes of treatment. One promising target highly expressed on kidney cancer cells is the enzyme, carbonic anhydrase IX (CAIX). Monoclonal antibodies (mABs) targeting segments on CAIX have had some beneficial treatment effects for patients in early phase clinical trials. As an enzyme, CAIX's exact role in the formation and spreading of kidney cancer cells is still being defined-and this sets the stage for the design of mABs with new and more effective anti-cancer properties.

Making mABs can be a tricky business, but that doesn't stop scientists Wayne Marasco, M.D.,Ph.D., and Quan Zhu, Ph.D., at the NFCR Center for Therapeutic Antibody Engineering in Boston. To develop novel CAIX mABs, Drs. Marasco and Zhu used a 27 billion human antibody phage display library previously established-a precious resource allowing selection and isolation of mABs against almost any molecular target on cell proteins.

Using cutting-edge selection procedures developed at the Center, the team isolated mABs that target the molecular segment of CAIX's enzyme function. Tests then confirmed that the new mABS inhibit the enzyme function of CAIX-a unique feature never obtained with other CAIX mABs.

The new mABs are valuable reagents for the development of new diagnostic tools to detect kidney cancer and immunotherapies for treatment. Because CAIX's enzyme activity has been linked to invasive properties of kidney cancer cells, these new mABs may inhibit the cell's ability to invade nearby normal tissues.

The Marasco and Zhu team knows that CAIX is a promising target for development of new mABs and have already developed a complex tumor model of kidney cancer for mAB evaluation. Testing is now being conducted in the model to confirm their unique mABs detect CAIX, inhibit its enzyme function, and stop the cancer from growing and spreading.

Developing novel anti-cancer mABs has become one of the most promising strategies for the treatment of cancer. While the Marasco and Zhu team were diligently designing and testing mABs targeting kidney cancer, the research community has demonstrated expression of CAIX in many other cancer types: breast, cervical, ovarian, lung, prostate, and other types of cancer. These unique CAIX mABs have the potential to become effective new diagnostic tools and treatment options-and have a significant impact on the care of many cancer patients.

Drs. Marasco and Zhu have recently published their work on these unique CAIX mABs in the journal PLOS One. To learn more, click here to visit the NFCR Center for Therapeutic Antibody Engineering website.