ABSTRACT
Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
Subject(s)
Humans , ADP-ribosyl Cyclase 1/immunology , B-Cell Maturation Antigen/immunology , Immunotherapy, Adoptive/methods , Multiple Myeloma/therapy , Receptors, Chimeric Antigen/immunology , Receptors, G-Protein-Coupled/immunology , Signaling Lymphocytic Activation Molecule Family/immunology , Syndecan-1/immunology , T-Lymphocytes/immunologyABSTRACT
multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
ABSTRACT
@#T cell receptor-engineered T cell (TCR-T) therapy is one of the hotspots in the field of cancer immunotherapy. Considerable achievements have been made since the first successful clinical trial in 2006. However, problems still remain in cytotoxicity, safety and persistence of TCR-T therapy despite the rapid development. Improving the immunosuppressive tumor microenvironment and enhancingchemotaxis, infiltration as well as activation of TCR-T cell will be the key to improve its anti-tumor effect. Neoantigens, which are highly tumor-specific and immunogenic,are the basis for safe and effective treatment and individualized cancer immunotherapy. Besides, infusion of less differentiated T cell subsets is also a reliable way to generate a long-lasting immune response. Here, combing with current research progress, we offer our perspectives on the current situation and challenges of TCR-T from the three aspects above.
ABSTRACT
CAR-T technology as a kind of immunotherapy, from the earliest generation of the first to the current fourth generation, its cytotoxic, anti-tumor immune effect greatly enhanced, but also challenged by safety issues.It shows a certain advantage in the therapy of Hepatocellular carcinoma. It indicates that the era of precise individual-ized liver cancer treatment, immune therapy, especially CAR-T technology combined with surgery, radiotherapy and chemotherapy, local treatment and other comprehensive treatment will play a more powerful role.
ABSTRACT
Objective To analyze the characterization of the target antigen of the monoclonal antibody(Mab) 03.2C1-C2 against germ tube of Candida albicans,and explore the possibility of Mab03.2C1-C2 application in the laboratory examination.Methods SDS-PAGE and Western blotting were used to analyse the molecular weight of antigens recognized by Mab03.2C1-C2.The distribution of the target antigens on the surface of the germ tube induced in vitro were analyzed.The epitope of the target antigen were analysed via indirect immunofluorescence(IIF).Results The target antigen recognized by Mab03.2C1-C2 could be detected 30 min after the germ tube formation.The distribution of the target antigens were different between the germ tube formated in vitro and in vivo.The epitope might locate in the N-carbohydrate chain.Conclusion New protein-glycoprotein that is the target antigen of Mab03.2C1-C2 was produced during the formation of the C.albicans germ tube.Strong antigenicity of glycoprotein is of certain value on quick diagnosis of Systemic C.albicans.
ABSTRACT
A group of glycoproteins with ⅥW 105- 130 K D from BHK-21 cell infected with Herpes Simplex Virus (HSV) were precipitated by six monoclonal antibodies (McAb). 1 A 12. Mad-2, 2D11, CM-D3, 2A8 and lC4,by using immunoprecipate technique. Im munoassays of BHK-21 cells infected with HSV-1/HSV-2 intertypic recom binants localized the genes encoding the target antigens of 1 A12, Mad-2, 2Dll, CM-D3, 2A8 and 1 C4 to the unique long region of HSV genesome at mapping unit 0.536—0.682 overlapping the gene encoding glycoprotein C(gC). De pending on reactivity with HSV- 1 and HSV-2 infected BHK-21 cells, Mad-2 shows HSV type-1 specificity, C M-D 3 shows HSV ty pe-2 specificity and the other four McAbs show type-common spe. cifity. So Mad-2 is against gC-1, CM D3 is against gC - 2 and 1 A12, 2 A8, 2 D11, 1 C4 are against type-common gC. We labelled the four McAbs directed at type-common gC with horseradise peroxidase (HRP)by the modified method of Nakane. ELISA blocking test was done to test the relationships of them. The result is that those four McAbs are against four distinct antigenic sites on type-common gC.