Clinical Trial Recommends New Cell Therapy for Relapsed Leukemia Patients

According to the researchers of the Stanford University School of Medicine and the National Cancer Institute. In a small study with the help of a new form of gene therapy, a significant proportion of young adults and children who participated in treatment-resistant B-cell leukemia achieved remission.

The senior author of the study is Mackall, professor of pediatrics and of internal medicine. It was published online in Nature Medicine.The lead author and led the conduct of the study at the institute is Terry Fry, MD, a pediatric hematologist and oncologist at the National Cancer Institute.

The therapy is similar to but distinct from CD19-targeted chimeric antigen receptor T-cell therapy, or CAR T-cell therapy, in which a patient’s T cells are genetically modified to target a molecule called CD19 on the surface of the cancer cells. FDA recently apposed this therapy for the treatment of some types of blood cancers.

This new therapy modifies a patient’s T cells genetically to target a different molecule called CD22. The new approach is beneficial for some patients, the cancer cells undergo CD19-directed CAR T-cell therapy stop expressing the CD19 molecule on the cell surface.In the phase 1 study, fifteen of the 21 patients who had previously either failed or relapsed to respond to anti-CD19 CAR T-cell treatment. It is currently used only when all other therapies have failed.

Crystal Mackall, MD, the associate director of Stanford’s Cancer Institute and the director of theParker Institute for Cancer Immunotherapy at Stanford said, “When we were first testing the CD19 CAR T therapy, this is the first time that we have seen response rates anything like we achieved. We were all a little worried that we wouldn’t find anything comparable. This study gives a hope to the concept that there may be another related study which is very potent treatment.” One that cancer cells are unable to avoid, researchers hope that targeting CD19 and CD22 together may result in a powerful therapy.

The most common cancer in children is B-cell acute lymphoblastic leukemia, and it’s usually successfully treated with chemotherapy. Nonetheless, patients who don’t respond to initial treatment, or after a successful remission whose cancer recurs, generally have a much poorer prognosis.

CAR T-cell therapy believes in a patient’s own T cells it is a type of immune cell that can be a powerful killing machine. To recognize specific molecules on the cancer cells’ surfaces and kill the cells, researchers genetically modify the T cells. Some long-term remissions have followed treatment with the CD19-targeted treatment.For the patients whose cancer cells don’t express CD19to avoid the treatment, either can relapse or don’t respond.Mackall and her colleagues wondered that could also be a good target if there was another molecule on the cancer cells. To test this idea her laboratory developed a novel CAR T-cell targeting CD22.

The phase 1, the study enrolled with patients 7 to 30 years of age for dose-escalation with B-cell acute lymphoblastic leukemia who received varying doses of the anti-CD22 CAR T-cell therapy.After the bone-marrow transplants, the participants who had either not responded or relapsed. Ten of the 15 patients who had already undergone CD19-targeted treatment no longer expressed any CD19 on the surface of their cancer cells.

One in six patients achieved complete remission after treatment at the lowest dose level with the anti-CD22 CAR T cells. Nonetheless, in the study when the researchers increased the dose to the next level, 73% or 11 of 15 patients, has entered the remission. Somewhat, the therapy was also well tolerated by the recipients.

The remissions lasted an average of six months, after the therapy only three patients remained in complete remission at 6, 9, and 21 months. Further, when the researchers investigated, they studied in those patients that cancer cells relapsed again they had begun expressing lower than normal levels of CD22 on their surfaces.

“Mackall said, the take-home message is that researchers found another CAR T-cell therapy that displays high-level activity in this phase 1 trial, but the relapse rate was also high. So this forces the field to get even more experienced. Mackall and Fry proved in in animal models and in the laboratory dish that T cell can kill cancer cells and they are testing it in a new clinical trial that has opened at Stanford and will clear soon at the National Cancer Institute.


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