Introduction: CAR-Ts recent breakthrough data in the field of self-exemption has made it "very popular"! According to the unknown media "fat Cat life medicine notes" estimates, their family fire! The next hit is its "cousin" —— BiTE, double specific T cell binder!
1、and the BiTE mechanism
BiTE is generated by bridging the targeted region of both antibodies. One arm of the molecule binds to the T cell surface CD3 protein, while the other arm binds to a specific protein.
When two targets are combined, BiTE molecules form a bridge between T cells and target cells, enabling T cells to recognize target cells and kill target cells by infusion of toxic molecules.
Does this look very familiar? Yes! It can make tumors, and can make free, please continue to see the analysis of the unknown authors!
2、BiTE, mainly for tumors
At present, there are many BiTE products on the market worldwide, and the main targets are CD19, BCMA and CD20. The main indications are in the field of hematology, including B cell related hematology, multiple myeloma, etc.
3、BiTE in the field of exemption "kill all sides"?
Today, talk with you to "gossip" about the application of BiTE in the field of self-exemption, an article on Nature Drug Disdovery makes xiaobian very exciting! Amgens BiTE, Blinatumumab may provide therapeutic hope for refractory wind-like knots.
Wind pass (RA) is a chronic inflammatory arthritis, is an autoimmune disease! Associated with circulating autoantibodies and pathogenesis. In most patients, advanced therapeutic drugs, including biological drugs (e. g., TNF inhibitors) and targeted small molecules (e. g., JAK inhibitors), are available.
B cells are considered as key mediators of RA pathogenesis, and the concept of B cell depletion as RA therapy is not new. CD20 antibodies were approved for RA treatment about 20 years ago. However, challenges remain, especially with innovative therapies for multiresistant or refractory RA. Then BITE stood up bravely.
Due to the limitations of rituximab, only 30% of RA patients achieved remission after treatment with rituximab and had significantly reduced responses in patients who had previously been treated with biologics. The reason for the difference in response rates is not fully understood and may be related to the difference in permeability of rituximab in tissues; in some patients, continued surviving CD20 + B cells remained in treated synovial tissue and antibody-generating CD19 + plasmablasts.
Blinatumomab is a CD19-CD3 BiTE that has been licensed for use in acute lymphoblastic leukemia but is not yet used for the treatment of immune-mediated inflammatory diseases.
Blinatumomab It consists of a CD3 antibody single-chain variable fragment (scFv) connected to the CD19 antibody via a flexible linker. By binding and activating CD3 + T cells, Blinatumomab "forces" T cells into cytotoxic killing of co-conjugated CD19 + B cells by perforin and granzyme, leading to B cell death. In leukemia clinical trials, Blinatumomab shows deep tissue penetration, even in relapsed patients. Therefore, the investigators speculate that it may be equally effective in other diseases mediated by B cells.
The investigators provided Blinatumomab treatment to six patients with multidrug resistant RA and ultimately observed a significant reduction in swelling and tender joint counts, along with improvement in objective measures of sonographic joint synovitis. Despite the dose lower than the therapeutic leukemia dose, the use of Blinatumomab in RA patients still had deep tissue penetration: two of the three patients that were sequentially sampled. Clinical response was also documented in a patient who had previously received rituximab therapy, where peripheral B cells were still depleted at the time of enrollment into the study.
The clinical response was essentially maintained at the 6-month follow-up, but one patient had persistent synovial CD20 + B cell infiltration after treatment, leading to disease recurrence, which could be a problem of dose optimization only. Moreover, the response to Blinatumomab therapy in a seronegative patient treated with rituximab was somewhat "unexpected"!
The findings suggest that Blinatumomab may "reset" the immune status of patients with RA. In this respect, it is similar to its cousin, CART! In patients with systemic lupus erythematosus (SLE), CART has very similar B cell clearance.
Although the trial results are encouraging, this is an open study that still requires double-blind, randomized controlled trials in formal registered clinics. Moreover, many questions remain about the safety of inducing long-term and deep B cell depletion in a non-fatal disease like RA.
But the potential for future research in RA and other B cell-mediated autoimmune diseases (such as systemic lupus erythematosus) is enormous! Will set off the next wave of wind and waves in the field of exemption!
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