March 28, 2022

Biologic and clinical efficacy of LentiGlobin for sickle cell disease

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featured discovery

Head shot of Dr. Julie Kanter, MD (Associate Professor, Hematology and Oncology), 2019.Julie Kanter, M.D.Julie Kanter, M.D., director of the UAB Adult Sickle Cell Clinic and associate professor in the Division of Hematology and Oncology, is the latest winner of the Heersink School of Medicine’s Featured Discovery. This initiative celebrates important research from Heersink faculty members.

Kanter’s study, “Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease,” was published in the New England Journal of Medicine.

In the study, Kanter and her team discuss outcomes from the use of LentiGlobin gene therapy for sickle cell disease. The report shows the success of the gene addition process by increasing the production of hemoglobin AT87Q and by decreasing severe vaso-occlusive crisis (severe, intermittent pain caused by sickle cell disease). Hemoglobin (Hb) is the protein in the red blood cell that carries oxygen. Sickle cell disease occurs when someone inherits an abnormal gene for hemoglobin, causing sickle hemoglobin or HbS.

Producing healthy hemoglobin production with LentiGlobin gene therapy could provide more effective treatment for this rare and painful disease.

“We are using genetic therapy to allow individuals with sickle cell disease to be their own donors,” said Kanter. “In other words, we can collect stem cells from someone with sickle cell disease and alter the genes in those cells to produce healthy hemoglobin.”

The team uses a viral vector (like an envelope) to deliver a gene to make healthy hemoglobin into the stem cells.

“We don’t change the genes in the stem cells, only add a gene that makes healthy hemoglobin,” said Kanter.

Read more from UAB News about Kanter’s work with LentiGlobin.

The Heersink School of Medicine communications staff sat down with Dr. Julie Kanter to gain insights about the research of this study, UAB, and the science community.

Q: What compelled you to pursue this research?

I have been focused on improving outcomes in sickle cell disease since I was a heme-onc fellow. We had few options and resources for people with sickle cell disease compared to cancer. In the last few years, I have also really focused on improving access to care for people living with sickle cell disease. We need to ensure that everyone with sickle cell disease has access to a sickle cell specialist. Some patients and doctors think if they don’t have a lot of pain, they don’t need a sickle cell specialist. However, sickle cell disease causes far more complications than pain alone and needs to be followed carefully so we can prevent complications.
I specifically started working in gene therapy many years ago when I led pediatric stem cell transplant and the Sickle Cell Center of Southern Louisiana. I had experience in both areas and wanted to offer this new potential for hope and improved outcomes in sickle cell disease. Gene therapy could change the paradigm for affected individuals making more definitive treatment more available for more people (as opposed to bone marrow transplant that requires a matched sibling).

Q: What was your most unexpected finding?

This is not my research alone by any means. I work with an amazing team from Bluebird Bio and researchers from all over the country, including the NIH. Together, we have had to modify the treatment in an iterative fashion since it started. Initially, the results were nearly as robust as they needed to be. We were very disappointed with these outcomes (in GROUP A). I was relieved when I learned the sponsor (Bluebird bio) would continue the study of sickle cell disease with new modifications. These new modifications (now our GROUP C) resulted in much improved outcomes and eventually this publication. I am not sure we have a “most unexpected finding,” but the most concerning finding is that two patients from group A later developed leukemia. We have not completely identified why this occurred. We know the new gene did not cause leukemia but worry that the stem cell transplant process (including stem cell harvest and chemotherapy) could have played a role and that some people with sickle cell disease could be at increased risk of leukemia. We are hopeful that the modifications made in group C have prevented other patients from getting leukemia are committed to answering these difficult questions.

Q: When did you know you had an important discovery?

Once we saw that the GROUP C patients enrolled in this study were making substantial amounts of healthy hemoglobin from the gene therapy (Called HbAT87Q), we knew this therapy could make a difference in people’s lives. We have now seen that the gene therapy almost completely resolves all of the hemolysis in the patients in group C and that no patients have had severe vaso-occlusive crisis since this therapy. We believe this therapy can really improve the quality and quantity of life in people with sickle cell disease.

Q: What made you come to UAB?

My long-term career goal is to ensure that every person with sickle cell disease (in the United States) has access to a sickle cell expert for their care. It is unfair that we will do whatever it takes for people with breast cancer to see an oncologist or people with cystic fibrosis to see a pulmonologist, but we do not hold sickle cell disease to the same ethical standard of care. I decided to come to UAB because I believed this University has a moral compass that points in the right direction-to truly improve care for people-especially those that cannot fight for themselves. I wanted to practice in a place where I could build a sickle cell center that could be nationally representative to improve outcomes in sickle cell disease. In meeting Dr. Landefeld and Dr. Bhatia (when I interviewed) and knowing the ongoing work in sickle cell disease at the Children’s of Alabama, I believed we could really move the needle forward in this lifespan disease.

Q: What do you find makes the science community here unique?

Since I have come to UAB, I find myself to be very lucky to be surrounded by other people motivated to improve outcomes in hard-to-reach populations. I have found academic friends - women - who support each other in ways that I never knew possible. I also found a hospital and University that can work together to make care better for people regardless of circumstance. I hope I continue to feel this way in another ten years, and I hope I can contribute to supporting young, driven academic clinicians to success. I especially hope to continue to provide support to other women who try and “do it all” with grace, knowing we have each other’s backs.