NFCR Center for Therapeutic Antibody Engineering

NFCR Supported Scientist Dr. Wayne Marasco Talks about the Translation of Tumor Research Discoveries

The Problem:

Among the most challenging questions in understanding cancer is how the immune system affects cancer development and progression. We now know our immune systems play a dual role in cancer: it can suppress tumor growth by destroying cancer cells or inhibiting their progression, but is can also promote tumor progression by selecting ‘more fit’ tumor cells or establishing microenvironment conditions that facilitate outgrowth.

The Solution:

The National Foundation for Cancer Research Center for Therapeutic Antibody Engineering (CTAE) is an antibody-engineering center affiliated with Dr. Wayne A. Marasco’s Laboratory in the Department of Cancer Immunology & AIDS of Dana-Farber Cancer Institute, a reaching hospital affiliate of Harvard Medical School. Lead by Dr. Marasco, researchers a CTAE have been focusing on targeted immunotherapy, treatment through engineered human antibodies. For cancer, as well as HIV/AIDS and other infectious diseases, one possible treatment involves the use of human monoclonal antibodies (mABs). Monoclonal antibodies are proteins that bind only to cancer cells through recognition of unique antigens. This biding then produces an immunological response against the cancer cell, generating tumor-fighting effects that are less harmful to normal cells than traditional cancer treatments.

The Research:

Dr. Marasco and his team recently developed new fmABs that have the potential to significantly impact diagnosis and treatment for kidney cancer patients, and for many other cancer patients as well.

The enzyme carbonic anhydrase IX, or CAIX, is highly expressed on kidney cancer cells and not on normal cells. This makes it a promising target for mABs. To develop novel CAIX mABs, Dr. Marasco and his team used a 27 billion human antibody phage display library, 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 for CAIX’s enzyme function, stopping the tumors from spreading.

The new mABs will help develop new diagnostic tools to detect CAIX on kidney cancer cells and immunotherapies for new anti-cancer treatments. 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.

While the Marasco team was 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.

In addition to designing and producing monoclonal antibodies for the development of anti-cancer therapies, Dr. Marasco’s team is discovering specific antibodies that target molecules that are critical in regulating human immune response against cancer. The Center also establishes tumor models for evaluation of identified therapeutic antibodies.

Impact on cancer detection, prevention and treatment:

The work of Dr. Marasco ad CTAE will continue to be useful in research studies and clinical trials for the treatment of cancer. CTAE is committed to establishing scientific collaborations and further adding to the 27 billion-member strong antibody library. Continued funding from NFCR will support the Center’s quest to find an immunological cure for multiple types of cancers.