2011 Research Grant

Antibody Conjugates for Targeted AML Therapy

Conducted by Dr. Hua Lu at the Scripps Research Institute.  Funded in Partnership with the Damon Runyon Cancer Research Foundation.

Dr. Hua Lu is working on the development of a new “antibody conjugate” technology to more precisely attack acute myeloid leukemia (AML) cells while leaving healthy cells intact.  If successful, the technology will be a major breakthrough both for improving survival and reducing side effects in AML and potentially other cancers as well.

Dr. Lu is a rising star in the field of chemistry and brings to his work a passion for finding better treatments for cancer and a novel idea for synthesizing ADCs. He is working in the lab of Dr. Peter Schultz (http://schultz.scripps.edu/main.php), a seasoned researcher and pioneer of breakthrough drug development techniques.

Hear Dr. Lu speak about his research and his motivation to fight back against cancer.

Dr. Lu is developing a unique technology that links molecules in very precise ways to an antibody, forming “antibody conjugates” that can recognize and kill cancer cells while leaving healthy cells unharmed.  Unlike conventional chemotherapy, antibody conjugates function like a biological GPS system to zero in on just the cancer cells, and when designed with precision, they have the potential for greatly reduced toxicity and improved survival. In addition to tracking down the cancer cells, Dr. Lu’s antibody conjugates work by bringing cells from the body’s own immune system to the disease site and activating them to kill the cancer.

Dr. Lu has successfully synthesized two “biFab” antibody conjugates intended to locate and bind to acute myeloid leukemia (AML) cells while at the same time binding and activating the patient’s own killer T-cells to destroy them. His tests on the first antibody conjugate showed a strong ability to bind to the AML cells. In further experiments, he examined cancer killing ability using an AML cell line and found that the antibody conjugate showed potent cancer killing as early as 24 hours post-incubation. The second antibody conjugate showed similar potency in killing AML cells.

Dr. Lu is now developing an animal model for testing the efficacy of the antibody conjugates and will perform a tumor reduction study using both of them. He will also test the two antibody conjugates in AML patient samples. Dr. Lu has made enormous progress and we are very excited about the promise his results hold for effective, low toxicity treatments for children with AML.

Why the research is so important 

One of the problems with conventional chemotherapy is that it kills cells indiscriminately, attacking not just cancer cells but healthy cells as well. By some estimates, only 1% of chemotherapy actually finds its target, the rest causing toxic side effects. Children in particular can suffer from serious and lifelong complications, including reduced heart function, respiratory damage, and diminished cognitive ability. Some treatments can even trigger a second cancer: the combination of chemotherapy and radiation used to treat Jake’s Hodgkin’s lymphoma was likely responsible for causing the AML which took his life.

Antibody conjugates are intended to overcome this problem by delivering drug directly and solely to disease cells, using an antibody as a biological “GPS system.” The goal is to more effectively attack the disease while leaving healthy cells unharmed.

However, initial attempts at developing antibody conjugates, particularly for AML, have fallen short because scientists have been unable to fully control how molecules attach to the antibody. Haphazard positioning can change the shape of the antibody or cover up the sites it needs to locate and bind to the cancer cells.  “Blinded” in this way, the conjugate fails to fully deliver its payload to its target and instead can cause harm elsewhere in the body.

Dr. Lu’s innovative technology is intended to create chemical “handles” to hold molecules in place, allowing the antibody to accurately find the cancer cells.

If successful, the technology could be used not just for AML but for the treatment of a variety of cancers.  The breakthrough would be especially important for children, whose still-developing systems would be spared chemo’s harmful effects, and who would be given a better chance at living full and healthy lives.

With this as our initial project, we’ve landed a solid first punch in the fight against pediatric cancer, for Jake and all the kids who today need better treatments and cures.