While immunotherapy has been successful for a number of aggressive cancers, acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes, has no currently known immunotherapy targets. In a recently published study in Nature Cancer, Arun Wiita, MD, PhD reports the hurdles and successes in developing a novel target using CAR-T cells developed specifically for AML.
Describe the work and explain how will this help patients or providers in the field
In this work we describe what we believe are two important advances that will benefit patients. First, we showcase a totally new technology to profile the 3-D shapes, or "conformations", of protein molecules on the surface of cancer cells. This technology is important because the most exciting new therapies in cancer engage the immune system to attack cancer cells based on these surface protein targets.
Numerous circulating blasts with monoblastic cytomorphology and gently folded nuclei. Image courtesy the American Society of Hematology.
Therefore, our technology ideally unlocks an entirely new class of immunotherapy targets based on protein shape. Second, we specifically develop a therapy targeting one of these protein shapes that is only present on tumor cells and not on normal cells. Our new therapy is designed to treat the deadly cancer acute myeloid leukemia, a disease that desperately needs new treatments. While much work remains to be done, the approach we describe has the potential to be turned into a real therapy to benefit patients.
“This new level of identifying and discriminating targets is an exciting advance not only for blood cancer but potentially any cancer, with the hope of developing safer, more effective therapies for patients.”
What excites you about this discovery?
We take advantage of an emerging technology called "CAR-T cells", where a patient's own immune cells are engineered to recognize and fight cancer. CAR-T cells have been very effective in some types of blood cancer, but for acute myeloid leukemia one of the major challenges has been the lack of surface protein targets on tumor cells that can allow for elimination of tumor cells while also sparing critical, normal blood cells.
We believe that the target we discovered here, called the active conformation of integrin beta-2, has the potential to overcome these prior hurdles and make a best-in-class safe and effective therapy. UCSF is one of the world's leaders in the development of T-cell engineering technologies. We thus have the knowledge, environment, and infrastructure at our institution to potentially turn this discovery into a true therapy that benefits patients.