Inner Ally

The use of the body’s own immune system to fight disease may be the future of safer and more precise cancer therapies

By Jim Daley
Joy Chong
Photo: Michael Goss

Targeted immunotherapy allows oncologists to design a new class of hunter-killer cells that can seek out and destroy cancer while leaving normal cells alone. The result is reduced toxicity compared to the currently available treatment such as chemotherapy and radiation therapy, and the potential for the highly effective cancer therapeutic method has been explored.

One area of immunotherapy that offers promise is the application of conjugated monoclonal antibodies. Antibodies are proteins that the immune system produces to identify and kill harmful pathogens by recognizing the unique molecular signature of that pathogen, called an antigen. A monoclonal antibody has been cloned from a parent cell and is expected to target and bind to the specific antigen expressed on cancer cancerous cells, thereby leading to death of the cancers.

Hyun-Sun Chong, a professor of chemistry at Illinois Tech, is developing antibody drug conjugates (ADCs) for targeted cancer therapy in her lab.

“The idea is to use a specific-tumor seeking antibody to load cytotoxic drugs or radiation to the targeted tumor site,” she says. “This selective targeting allows a therapeutic drug or radiation to be safely delivered to cancer cells, while minimizing damage to normal healthy cells.”

Chong’s interdisciplinary research laboratory is currently focused on the development of anti-cancer drugs and utilization of radiation and antibody combinations in preclinical studies. The process starts by designing and producing drug candidates and then screening them against human cancer cell lines in her lab. Promising drugs can then be conjugated to a tumor-specific antibody for generation of ADCs for detailed preclinical studies. In collaboration with other researchers in medical schools, the best antibody-drug conjugates will be investigated for their effectiveness in removing tumors in animal models.

She says that this therapeutic approach has improved the efficacy and safety of traditional therapies such as chemotherapy and radiation therapy and has been utilized for development of personalized cancer drugs, particularly in the area of ADC pharmaceuticals and radioimmunotherapy (RIT), in which the conjugated antibody is attached to a radioactive isotope designed to kill cancer cells.

“The RIT technology is a safer and more potent way to deliver radiation to cancer cells but has been limitedly applied to the clinic,” Chong says. “To develop clinically viable RIT drugs, it is essential to use optimal chelation chemistry to sequester a therapeutic radioactive metal rapidly and tightly. A radioactive metal has a limited half-life, ranging from hours to days, and efficient generation of RIT drugs is critical. A premature release of a radioactive metal from less stable RIT drugs will lead to a long-term toxicity, including bone marrow toxicity. We design and study chelation chemistry by controlling a combination of parameters for the generation of stable RIT drugs with high in vivo stability and blood clearance.”

Chong is also investigating the application of chelation chemistry to generate antibody conjugates for detecting cancers using positron emission topography (PET) imaging technology. In this technique, a radioactive imaging probe bound to an optimal chelate is attached to an antibody. The radiolabeled antibody conjugate targeting a specific tumor site is injected into the live animals. The radiolabeled antibody conjugates are localized to cancerous cells present in the patient that can be detected and imaged by the PET scan. The highly sensitive PET can detect cancer that other imaging techniques might miss and also monitor the effectiveness of ongoing treatments.

Since 2004 Chong’s research on antibody-targeted cancer therapy and imaging has been continuously supported by more than $2 million in grants from the National Institutes of Health. Her work has thus far led to two United States patents being issued and an additional two U.S. patent applications. Additionally, Chong’s lab is discussing transfer of ADC/RIT technology for clinical applications to realize safe and potent targeted cancer therapy and imaging.

Chelation chemistry is the study of how molecules bind to one another in a chelate complex. The word chelate comes from the Greek chēlē, meaning “claw,” and refers to the strength of the bond. Chelation chemistry has applications ranging from microbiology and cancer therapy to geology and agriculture.