Xianxin Hua, MD, PhD

Imagine packing a two-micron-long molecule into a container thousands of times smaller than a tiny section of human hair. This describes nanotechnology, which Xianxin Hua, MD, PhD is employing to arm and deliver an innovative acute myeloid leukemia (AML) treatment—biCAR T. The approach packs chimeric antigen receptor (CAR) mRNA in lipid nanoparticles (LNPs) to target CD13/TIM3—two cell surface proteins on antibodies upregulated in the blood cancer.

Rare and aggressive, AML develops when defective white blood cells created in the bone marrow multiply, crowding out healthy red blood cells and white blood cells necessary for supplying oxygen and fending off invaders. Individuals may mistake chronic tiredness, dizziness, bone pain, and frequent infections for flu that doesn’t go away. For some of the nearly 150,000 diagnosed annually, treatment arrives too late.

While chemotherapy achieves remission rates of 60-80% in younger patients, rates in older patients are lower (30-50%). In certain patients, AML is refractory—unresponsive. Relapsed and refractory patients have few effective therapy options—they need a readily available, effective, and less toxic alternative. Dr. Hua’s nanotechnology approach would eliminate costly and time-consuming conventional in vitro CAR T manufacturing steps by packaging CD13/TIM3-targeting CAR mRNA (bi CAR) into lipid nanoparticles (LNP) and then injecting the mRNA/LNP cargo directly into a patient’s body. When biCAR is expressed in the patient’s T cells, it specifically seeks and destroys AML stem cells carrying CD13 and TIM-3 receptors while sparing normal cells and reducing toxicity.

“We demonstrated proof of concept in vitro,” Dr. Hua says. “Next, we will test human cell-derived biCAR T in mice, and if that’s successful, we will test in larger animals, then move to clinical trials in humans.”

Dr. Hua envisions the biCAR T treatment readily available worldwide for most AML patients, regardless of age and disease stage.

“A scalable, off-the-shelf product has potential to transform CAR T cell therapy for AML.”