CELL INTELLIGENCE · 肿瘤细胞治疗研究

Acute lymphoblastic leukemia (ALL) is the most common cancer in the pediatric population, and the long-term survival can reach 90%. However, approximately, 20% of pediatric ALL patients experience relapse and require second-line chemotherapy. This is frequently followed by hematopoietic stem cell transplantation, which can cause long-term sequelae. Recent advances in immunotherapy, such as monoclonal antibody therapy and chimeric antigen receptor (CAR)-T cell therapy, have revolutionized the treatment of relapsed and refractory ALL. Anti-CD19 CAR-T cells successfully eliminate B cell malignancies such as ALL. Tisagenlecleucel (Kymriah ) is the first CAR-T cell immunotherapy approved by the FDA. CAR-T cell therapy can cause specific adverse events (AEs) such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which are defined and graded according to the consensus grading system and treated with supportive therapies along with tocilizumab and corticosteroids. Other AEs include prolonged bone marrow suppression and hypogammaglobulinemia. Severe AEs are less common in the real-world experience than in clinical trials, probably due to better management of the patient before and during CAR-T cell therapy. The biggest challenge in CAR-T cell therapy against ALL is relapse. A high tumor burden on infusion, early loss of B cell aplasia, and minimal residual disease positivity after CAR-T cell infusion are predictive of relapse. Consolidative stem cell transplantation may improve the long-term outcome. The success of CD19 CAR-T cell therapy against B cell malignancy prompted extensive research into the use of CAR-T cells against other hematologic malignancies such as T cell leukemia or myeloid leukemia.