Genetically engineered immune cells successfully target specific cancer cells that may be responsible for relapse of acute myeloid leukemia (AML), a type of blood cancer, and have been shown to be effective in animal models of the disease, according to a preclinical study by Weill Cornell researchers. medicine.
The new cell therapy, which is now being tested in Phase I clinical trials, may eventually help patients with acute myelogenous leukemia (AML) remain cancer-free.
In the study, published April 28 in Nature Communications, the researchers used an approach in which immune cells known as T cells are directed to produce proteins called chimeric antigen receptors, or CARs, that enable T cells to recognize specific markers on cancer cells. In this case, CAR is a receptor that binds to the CD123 molecule on leukemia stem cells, enabling T cells to seek out and attack cancer cells.
Co-lead author Monica L. Guzman is a member of the Sandra and Edward Mayer Cancer Center at Weill Cornell Medicine. “CD123 is a marker found on leukemia stem cells, and my lab is working on designing mouse models to test new therapies targeting CD123 to fight leukemia.”
Although there are effective treatments for acute myelogenous leukemia (AML), the disease eventually recurs in most patients even after complete remission has been achieved. By engineering T cells to express CAR that targets CD123, Guzman and her colleagues hope to rid patients of any remaining leukemia stem cells. CAR T cells are an attractive anticancer treatment because they can be grown in large numbers in the laboratory.
“The CAR T cells — called UCART123 cells — used in this study have several very important features,” Guzman said. “They target a marker of leukemia stem cells, they’re derived from healthy donors and they’re manufactured to be ‘off the shelf’ and ready for patients when needed, they’re specifically designed to try to reduce toxicity, and they can be eliminated with a drug called rituximab in case of overproliferation.”
When the team tested UCART123 cells in a mouse model of AML, they found that the treatment effectively eliminated leukemia cells and extended survival time. The scientists also designed a highly sensitive surveillance strategy to detect any remaining cancer cells and to assess the viability of UCART123 cells. Finally, they showed that UCART123 cells have specificity against leukemia cells, with minimal toxicity to normal blood cells in mice.
Preclinical findings have led to a Phase I clinical trial test UCART123 In patients with relapsed/refractory AML at several locations across the United States, including NewYork-Presbyterian/Weill Cornell Medical Center. “These in vitro data strongly support the ongoing clinical trial,” said lead researcher on the trials and co-first author Dr. .
“The results of the preclinical study indicate that UCART123 cells are highly selective and specific in targeting AML, and we expect that the technologies developed in Dr. Guzman’s lab will help us monitor patients undergoing treatment with UCART123 and improve their likelihood of success,” he said. Robbose, who is also a professor of medicine in the division of hematology and medical oncology and a member of the Mayer Cancer Center at Weill Cornell Medicine.
Many physicians and scientists at Weill Cornell Medicine maintain relationships and collaborate with outside organizations to advance scientific innovation and provide expert guidance. The Foundation publishes these disclosures publicly to ensure transparency. For this information, see the profiles of Monica Guzman And the Dr. Jill Roboz.
Tracy Hampton is a freelance writer for Weill Cornell Medicine.