ABSTRACT
The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.
Subject(s)
Humans , Cell- and Tissue-Based Therapy , Immunotherapy, Adoptive , Lymphoma/therapy , Receptors, Antigen, T-Cell , Receptors, Chimeric AntigenABSTRACT
@#Due to the spectacular therapy results in hematologic tumors, chimeric antigen receptor T (CAR-T) cell therapy has been the research hot-spot in the field of cell-immunotherapy. Viral vectors, as the critical raw material in CAR-T cell manufacturing, are closely related to the safety, efficacy and quality control of CAR-T cell products, in the aspects of the structure design of CAR gene, refinement of production process, quality control and setting of characterization and specification etc. Based on the research progress in lentiviral and γ-retroviral vectors development and the evaluation experiences, this paper discusses some common problems that need to be focused on in the preparation of viral vectors, expecting to provide references for the development and the authorization applications of domestic related products in the future.
ABSTRACT
@# CAR-T cell therapy has developed rapidly in recent years, and has achieved amazing results in the treatment of some malignant tumors of the blood system, but little progress has been made in the treatment of solid tumors. At present, the main problems to be solved in CAR-T cell therapy are: (1) enhancing the killing activity of CAR-T cells; (2) relieving the immunosuppressive state of tumors; (3) bringing CAR-T cells into solid tumors; (4) enhancing the safety of CAR-T cell therapy. By optimizing the structure of CAR, a series of defects in the CAR-T cell therapy can be overcome, and the curative effect of CAR-T can be enhanced and the complications can be alleviated. In this paper, some optimization and improvement measures and methods on the structure design of CAR in recent years are elaborated, and the effectiveness and safety of the CAR-T cell therapy are explored.