β-thalassemia is a hereditary blood disorder caused by mutations in the β-globin gene, leading to impaired synthesis or structural changes in β-globin. Gene therapy for β-thalassemia using lentiviral vectors refers to a gene integration strategy where a fully functional β-hemoglobin gene is added to the chromosome using lentiviral vectors. Currently, gene integration strategies have undergone various stages of clinical trials worldwide, and several patients have become independent of blood transfusions, showing promising prospects. However, the high treatment cost remains a significant barrier to the widespread adoption of this strategy.
From January 5th to 7th, 2024, the 4th China Hematology Development Conference (CASH) opened grandly in Tianjin. Professor Jun Shi from the Institute of Hematology of the Chinese Academy of Medical Sciences presented an intriguing report on “Gene Therapy for β-Thalassemia Using Lentiviral Vectors.” In an interview with “Oncology Frontier – Hematology Frontier,” he discussed the current situation of β-thalassemia diagnosis and treatment in China, as well as the research progress in using lentiviral vectors for treating β-thalassemia.
“Oncology Frontier – Hematology Frontier“: β-thalassemia is the most common congenital anemia among Asians. Could you please talk about the current prevalence and treatment status of β-thalassemia in China?
Professor Jun Shi : β-thalassemia is a distinctive disease distributed along the “Belt and Road Initiative” route. It is mainly found in regions such as Guangxi, Guangdong, Yunnan, Guizhou, and Sichuan in China. According to the Thalassemia Blue Book report, there are currently approximately 300,000 patients in China with severe/transfusion-dependent thalassemia (TDT), and there are also intermediate-type patients. The prevalence of the disease is increasing at a rate of 10% per year. The prevalence in the Guangdong-Guangxi region ranges from 5% to 15%. Regarding the current diagnosis and treatment status of thalassemia, about 1/5 of the patients have the conditions and capabilities to undergo allogeneic hematopoietic stem cell transplantation, while the remaining 4/5 of the patients generally receive blood transfusions and specific drug treatments. Additionally, nearly 60% of patients cannot access blood transfusions because of the severe shortage of blood products in our country. For patients diagnosed with severe β-thalassemia, blood transfusion plans are recommended when hemoglobin is below 90 g/L, and transfusions are administered only when hemoglobin is above 90 g/L to ensure normal growth and development. However, clinical practice often delays transfusion until hemoglobin falls below 60 g/L, posing the most significant challenge in current diagnosis and treatment.
“Oncology Frontier – Hematology Frontier“: In your presentation at this conference, you discussed “Gene Therapy for β-Thalassemia Using Lentiviral Vectors.” Could you please introduce the principles, safety, and efficacy of this treatment?
Professor Jun Shi : β-thalassemia (β-thalassemia) is a hemolytic anemia caused by mutations in the β-hemoglobin (HBB) gene and is the most common monogenic genetic blood disorder worldwide. The primary principle of treating β-thalassemia is to combine gene therapy with autologous hematopoietic stem cell transplantation to correct the anemic phenotype and suppress ineffective red blood cell production. Using lentiviral vectors (LVV) to introduce the viral sequence of the fully functional HBB gene into hematopoietic stem cells allows these cells to differentiate and establish the proper ratio of α and β hemoglobin, thereby increasing the patient’s hemoglobin levels. After introducing hematopoietic stem cells with the viral vector, we typically employ a preparatory regimen of toxic chemotherapy for patients, clearing their bone marrow microenvironment. Then, we reinfuse the hematopoietic stem cells processed by the viral vector, allowing them to engraft into the bone marrow microenvironment and exhibit their hematopoietic differentiation capabilities, aiming to achieve clinical cure.
“Oncology Frontier – Hematology Frontier“: Treatment with thrombopoietin receptor agonists (TPO-RAs) for bone marrow failure diseases has been a recent research hotspot. Could you please discuss the latest developments in this area?
Professor Jun Shi : The most significant advancement with TPO-RAs is the substantial improvement in the efficacy of treating aplastic anemia when used in conjunction with existing drug therapies. Aplastic anemia, especially severe aplastic anemia, is primarily treated with a first-line standard therapy involving immunoglobulins, anti-lymphocyte globulin, and cyclosporine, with an effective rate of 50% to 60%. When combined with TPO-RAs, the effective rate can be increased to 80% or even above 90%, allowing more patients to gradually become independent of blood transfusions.
Professor Jun Shi currently holds the position of Vice Dean at the Institute of Hematology, Chinese Academy of Medical Sciences, and Peking Union Medical College Hospital. He also serves as the Deputy Director of the National Clinical Research Center for Blood Diseases, the Director of the Center for Regenerative Medicine, and the Director (concurrently) of the Anemia Diagnosis and Treatment Center.
Professor Jun Shi has been involved in various roles, including being a member of the Hematology Specialty Committee of the Chinese Medical Association, Deputy Head of the Red Blood Cell Diseases Group, a member of the Blood Physiology Specialty Committee of the Chinese Physiological Society, a member of the Internal Medicine Branch of the Chinese Medical Doctors’ Association, an editor for the Chinese Journal of Hematology, Vice Chairman of the Tianjin Medical Association Hematology Specialty Committee, a member of the Tianjin Medical Association Council, and the leader of the China Hematology Specialized Alliance—Rehabilitation Collaboration Group.
His primary areas of focus include basic research in hematopoietic regeneration and clinical translational research. He conducts extensive research on gene therapy for β-thalassemia, the molecular pathological mechanisms of bone marrow failure and autoimmune diseases, and clinical treatment interventions.
