Breakthrough in Global First-in-Class Autologous CD7-CAR-T Therapy for Relapsed/Refractory T-ALL/LBL

Recently, Bo Sheng Ji revealed on its official WeChat account that its CD7-CAR-T cell therapy for the treatment of refractory and relapsed T-cell acute lymphoblastic leukemia/lymphoma has achieved a breakthrough in clinical trials.

It is understood that CD7-positive malignancies are predominantly highly aggressive lymphomas or leukemias, characterized by rapid disease progression and poor prognosis, with most cases experiencing relapse shortly after achieving remission through chemotherapy. These diseases primarily include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), extranodal NK/T-cell lymphoma, as well as various rare and orphan diseases. For the treatment of refractory and relapsed T-ALL/LBL, only nelarabine has been approved by the U.S. FDA internationally; however, the complete remission (CR) rate achieved with nelarabine is merely 20%–30%, and the median overall survival for patients receiving monotherapy is only 8 months. CD7-CAR-T cell therapy aims to provide a superior treatment option for refractory and relapsed T-ALL/LBL.

However, unlike traditional CD19-CAR-T and BCMA-CAR-T therapies, the development and clinical application of CD7-CAR-T cells face significant challenges. These include the co-expression of CD7 on both tumor T cells and normal T cells, which leads to fratricide among CAR-T cells during conventional manufacturing, thereby preventing their successful production; the risk of residual tumor T cells in the final CAR-T product, which precludes product release; and the potential for transient T-cell lymphopenia, increasing the risk of infection. Internationally, numerous studies are exploring strategies based on gene editing to knock out CD7 and the T-cell receptor (TCR) for the preparation of universal CAR-T (UCAR-T) cells from healthy donors. In contrast, BoShengJi’s autologous CD7-CAR-T cells avoid the risks associated with gene editing and demonstrate favorable prospects for therapeutic efficacy, supported by robust in vivo expansion and persistence.

In clinical studies, CD7-CAR-T cells prepared from peripheral healthy T cells of patients exhibited superior cytotoxic activity against CD7+ malignant target cells, effectively killing tumor cells even at an effector-to-target ratio as low as 1:100.

In PDX models established from patient-derived primary T-ALL cells, CD7-CAR-T therapy significantly prolonged survival (left panel); analysis of major organs with tumor burden revealed near-complete clearance of tumor cells (right panel).

The study enrolled patients with refractory and relapsed T-cell lymphoblastic leukemia/lymphoma at Stage VI. Representative clinical data showed that on Day 28 after CAR-T cell infusion, the patient achieved complete remission with minimal residual disease (MRD) negativity in the bone marrow. There was a significant reduction in the number of lymph nodes in the nasopharynx, neck, bilateral axillae, hilar regions, and bilateral inguinal areas, accompanied by marked decreases in volume and metabolic activity (see figure below). On Day 90 after CAR-T cell infusion, the patient achieved complete remission.

In this report, the first three patients achieved an overall response rate (ORR) of 100%, with two patients attaining complete remission and one patient achieving partial remission. More importantly, none of the three patients experienced neurotoxicity; cytokine release syndrome (CRS) was grade 2 in one patient and grade 1 in two patients. Further detailed results from this clinical trial will be presented as an oral presentation at the 2020 European Hematology Association (EHA) Congress.

Meanwhile, BoShengJi stated that larger-scale clinical trials of its CD7-CAR-T cell therapy are currently underway, and the Investigational New Drug (IND) application is in the final countdown.