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
Resumen El glioblastoma es uno de los tumores primarios del sistema nervioso central más agresivos, debido a su alta capacidad de generar resistencia a la mayoría de los tratamientos oncológicos disponibles actualmente. Asimismo, este tumor tiene un elevado potencial de recidiva y genera una mortalidad alta entre los individuos afectados. Por lo tanto, existe una urgente necesidad por contar con nuevas estrategias terapéuticas que permitan lograr una mayor tasa de remisión y una mejor sobrevida en los pacientes con glioblastoma. Novedosos avances en inmunoterapia, como la generación de linfocitos T autólogos modificados por ingeniería genética, prometen ser agentes terapéuticos capaces de proveer un grado considerable de control sobre diferentes tipos de cánceres. En el presente artículo, se comentan los resultados de algunas investigaciones recientes sobre el uso específico de esta estrategia para el manejo de individuos con glioblastoma.
Abstract Glioblastoma is among the most aggressive primary tumors of the central nervous system due to its high capacity to acquire resistance to many of the currently available oncologic treatments. Likewise, this tumor possesses an elevated potential for recurrence generating a high mortality among affected individuals. Therefore, there is an urgent necessity for new therapeutic strategies to achieve a higher remission rate and a better survival rate in patients with glioblastoma. New advances in immunotherapy, such as the production of autologous T lymphocytes modified by genetic engineering, are promissory therapeutic agents capable of providing a considerable degree of control over different types of cancers. In this article, we discuss the results of some recent studies
ABSTRACT
@# Chimeric antigen receptor modified T (CAR-T) cell therapy is one of the important methods of tumor immunotherapy. The targeting, killing, proliferation and persistence of CAR-T cells are significantly enhanced than that of conventional T cells.After continuous improvement and evolution, CAR-T cell treatment has achieved excellent progress in hematological tumors and has received extensive attention. However, neurotoxicity arising from the treatment, also known as CAR-T cell relevant encephalopathy syndrome (CRES), has affected its clinical application. Exploring the pathogenesis of CRES and high-risk factors, and finding appropriate strategies is therefore critical for the prevention and treatment of CRES. Here, we take CD19-CAR-T cell treatment as example to review the symptoms and pathogenesis of CRES, discuss high-risk factors as well as coping strategies, in an effort to provide a reference for clinical treatment.
ABSTRACT
Chimeric antigen receptor modified T cell (CAR T) cytotherapy is a modified technology of T cell immunotherapy. It has achieved encouraging breakthroughs in the treatment of hematological malignancies. Recent studies had shown that CAR T cells can also be used in the treatment of solid tumors. However, it′s indispensable to understand its bottlenecks, including regulating CAR T cell expansion, survival time, metastasis, and prognosis in vivo, to establish a feasible and effective CART-based solid tumor therapy model. Therefore, we summarized the advances, challenges and possible solutions for CAR T therapy to treat solid tumors, and then prospected in the future clinical treatment.
ABSTRACT
@#Chimeric antigen receptor modified T (CAR-T) cell therapy has achieved excellent clinical efficacy in patients with hematological malignancies (especially for patients with CD19 positive), and is regarded as a major advance in cancer therapy in recent years. It aroused scientists’strong interest in developing CAR-T cell products for the treatment of cancers. However, there are still some problems in the treatment of CAR-T cells. For examples, some patients lose the opportunity of CAR-T cell therapy while waiting for CAR-T cell culture, some unique adverse events during treatment of CAR-T cell therapy may endanger the patients’life, and the efficacy of CAR-T cell therapy is unsatisfactory on solid tumors. Even for hematological malignancies, some patients will eventually relapse and lead to treatment failure. Therefore, exploring methods to improve the efficacy, diagnosis the unique adverse events of CAR-T cell therapy early and give appropriately management, expand potentially benefiting populations of CAR-T cell therapy are issues that need to be addressed in current CAR-T cell therapy research.
ABSTRACT
@# Due to the long-lasting, scalable, multi-targeting characteristics of T-cell immunity, T-cell-based tumor immunotherapy is considered to be the most likely means of bringing about tumor healing in addition to surgery. Especially in recent years, accumulating clinical data have confirmed the safety and effectiveness of cell therapy represented by chimeric antigen receptor modified T (CAR-T) cell. Among these, CAR-T therapy targeting CD19 has become a model therapy for genetic modified T cell therapy research in most institutions because of its remarkable effects. However, both practice and theory have suggested that CAR-T therapy faces more complicated problems in the treatment of solid tumors. How to use CAR-T cells to treat solid tumors reasonably and effectively still requires constant exploration and understanding. Here, we briefly summarize the current status of clinical practice of CAR-T cell therapy and its treatment of solid tumors, propose problems that need to be solved, and discuss the future research directions, in order to provide reference and research ideas for the treatment of solid tumors by CAR-T cells.
ABSTRACT
@#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.
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@# 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.
ABSTRACT
Osteosarcoma( OS) is one common type of bone malignancy. Conventional treatments improved survival dramatically. However, conventional therapies have a few effects on patients with metastatic disease. Targeting os-teosarcoma-associated antigen, chimeric antigen receptor-modified T cell( CAR-T) therapy may promote efficacy of treatment. Specific CAR-T treatments of osteosarcoma including targeting HER-2, IL-11Rα, ROR1 and GD2 have shown a certain therapeutic effect on osteosarcoma in some basic and clinical studies.