A New Trial Demonstrates Promising Results of CAR T Targeting CD-22 for Leukemia Patients.

The Treatment is Not A New Way as Being Stated, It is Only the Target, Which Has Been Changed  

Outstanding news announced that leukemia patients who relapsed after being treated with the chimeric receptor antigen T cell (CAR T) targeting CD-19 were saved from imminent death by a CAR T targeting CD-22. The new treatment, which is being presented in some articles as a new way of treatment is not another immunotherapy approach. The approach is still CAR T except for the fact that the CAR T target in the new trial has been CD-22 instead of CD-19.

The new experimental treatment could eventually be given as monotherapy or in combination with the CAR T targeting CD-19 so as to increase the odds against cancer relapses.   

Two CAR T targeting CD-19 are already approved by the FDA. These are Kymriah and Yescarta.

Kymriah, owned by Novartis, is prescribed for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or relapse following conventional treatments.

Yescarta, which was created and developed by Kite Pharma, now belongs to Gilead Sciences after acquiring Kite. The CAR T product  Yescarta is approved for Non-Hodgkin’s Lymphoma.

The Story

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

The new therapy genetically modifies patients’ T cells to target a different molecule called CD22.

The new approach is helpful because some patients who undergo CD19-directed CAR T-cell therapy stop expressing the CD19 molecule on the cell surface.

Fifteen of the 21 patients in the phase-1 study had previously either relapsed or failed to respond to anti-CD19 CAR T-cell treatment, which is currently used only when all other therapies have failed.

The New Study Brings Hope

“This is the first time that we’ve seen response rates anything like we achieved when we were first testing the CD19 CAR T therapy,” said Crystal Mackall, MD, associate director of Stanford’s Cancer Institute and the director of the Parker Institute for Cancer Immunotherapy at Stanford. “We were all a little worried that we wouldn’t find anything comparable. But this study gives hope to the idea that there may be another similar, very potent treatment.”

Researchers hope that targeting CD19 and CD22 simultaneously may result in a powerful therapy — one that cancer cells will not be able to evade.

Mackall, the professor of pediatrics and of internal medicine, is the senior author of the study, which was published online Nov. 20 in Nature Medicine. Terry Fry, MD, a pediatric hematologist and oncologist at the National Cancer Institute, is the lead author and led the conduct of the study at the institute.

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

In CAR T-cell therapy researchers genetically modify the T cells to recognize specific molecules on the cancer cells’ surfaces and kill the cells. Some long-term remissions have followed treatment with the CD19-targeted treatment. Patients who do not respond to CD-19 targeting CAR T therapeutics are those whose cancer cells do not express CD19, or which tamp down their expression to evade the treatment, either don’t respond or can relapse.

Mackall and her colleagues wondered if there was another molecule on the cancer cells that could also make a good treatment target. To test this idea, Mackall’s laboratory developed a novel CAR T-cell that targets CD22.

The phase-1, dose-escalation study enrolled patients ages 7 to 30 with B cell acute lymphoblastic leukemia who received varying doses of the anti-CD22 CAR T-cell therapy. Each of the participants had either not responded at all to the anti CD-19 CAR T or relapsed after bone-marrow transplants, and 10 of the 15 patients who had already undergone CD19-targeted treatment no longer expressed any CD19 on the surface of their cancer cells.

Dosing and Escalation

At the lowest dose level, one in six patients achieved complete remission after treatment with the anti-CD22 CAR T cells. However, when the dose was escalated to the next level in the study, 73 percent, entered remission. The therapy was also relatively well-tolerated by the recipients.

The remissions lasted a median of six months; three patients remain in complete remission at six, nine and 21 months after the therapy. When the researchers investigated further, they learned that cancer cells in those patients who had relapsed had begun expressing lower-than-normal levels of CD22 on their surfaces.

Bottom line, here we are with another CAR T-cell therapy that displays high-level activity in this phase-1 trial

Mackall remarked, “But the relapse rate was also high. So this forces the field to get even more sophisticated. How much of a target is needed for successful, long-lasting treatment? What happens if we target both CD19 and CD22 simultaneously?”

The researchers are already tackling the last question by testing a CAR T cell that recognizes both CD19 and CD22. They have now confirmed that this T cell can kill cancer cells in the laboratory dish and in animal models, and they’re testing it in a new clinical trial that has opened at Stanford and will open soon at NCI.

The work was also supported by the NIH, St. Baldrick’s Foundation and Stand Up 2 Cancer, Stanford’s departments of Pediatrics and Medicine.

Prohost Observations

Again, we continue to repeat that the CAR T approach to cancer treatment is here to remain and improve and continue to save lives. The few companies specialized in this genetically engineered cells’ treatments already amassed a huge experience that would continue to help them improve on their CAR T treatment and increase the treatment reach to many other cancers, including solid tumors. These firms now comprise Novartis (NVS) and Gilead (GILD), which also has an approved CAR T and the Kite team that is running the show of developing the genetically engineered treatments and continue to do the same as part of Gilead Sciences.

Other firms include Juno (JUNO), Cellectis (CLLS), Celyad (CYAD) and Bellicum (BLCM). These three biotech Companies aim at making non-autologous, over the shelf CAR T products. Celyad has investigational CAR NK products in clinical trials.

We will continue to feed the reader about these firms’ trials and achievements.

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