Anti-bcma car t cell compositions
A composition, B cell technology, applied in DNA/RNA fragments, drug combinations, extracellular fluid diseases, etc., can solve the problem of immature enough to predict the effective dose of CART cells for treatment, etc.
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example 1
[0171] Construction of BCMA CAR
[0172] A CAR containing a mouse anti-BCMA scFv antibody was designed to contain the MND promoter operably linked to the anti-BMCA scFv, the hinge and transmembrane domains from CD8α, and the CD137 co-stimulatory domain, followed by the intracellular signaling of the CD3ζ chain conduction domain. see for example figure 1 . figure 1 The shown anti-BMCA CAR includes a CD8α signal peptide (SP) sequence for surface expression on T cells. The polynucleotide sequence sequence of exemplary anti-BMCA CAR is listed in SEQ ID NO:10; The exemplary polypeptide sequence of anti-BMCA CAR is listed in SEQ ID NO:9; And figure 1 Vector maps of exemplary CAR constructs are shown in . Table 3 shows the identity, Genbank reference, source name and citation of various nucleotide segments of the anti-BMCA CAR lentiviral vector.
[0173] table 3.
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example 2
[0177] Anti-BCMA CAR T cell manufacturing process
[0178] Create a unique anti-BCMA02 CAR T cell product for each patient regimen. The reliability of the manufacturing process of the anti-BCMA02 CAR T cell product was assessed by generating anti-BCMA02 CAR T cells from 11 individual normal donor PBMCs. Anti-BCMA02 CAR T cell expansion from each donor was compared to matched non-transduced cultures performed in parallel ( Figure 2A ).
[0179] At the end of the culture period (day 10), T cell transduction efficiency (vector copy number VCN) was assessed by quantifying the number of integrated lentiviruses using qPCR and a lentivirus-specific primer set. Anti-BCMA02 CAR T cell cultures from 11 donors showed comparable lentiviral transduction efficiencies ( Figure 2B ). The frequency of anti-BCMA02 CAR-positive T cells was measured by flow cytometry, and BCMA expression was found to be comparable in all donors ( Figure 2C ).
[0180] The activity of each anti-BCMA02 CAR...
example 3
[0182] Anti-BCMA02 CAR T cells show therapeutic activity in a human clinical trial for relapsed / refractory multiple myeloma
[0183] introduce
[0184] Chimeric antigen receptor (CAR) T-cell therapy has demonstrated robust and sustained clinical responses observed in several hematological malignancies. Beyond CD19, however, clinical data supporting the promise of CAR T cells remain limited. To test the potential for the safety and efficacy of CAR T cells in relapsed / refractory multiple myeloma (MM), a patient population with limited treatment options. To redirect T cells to MM, we targeted B cell maturation antigen (BCMA), a member of the tumor necrosis factor superfamily expressed almost uniformly only by malignant myeloma cells, plasma cells, and some mature B cells. Preliminary evidence of anti-BCMA activity has recently been demonstrated using T cells transduced with a gamma retroviral vector encoding an anti-BCMA CAR with a CD28 co-stimulatory domain, but patients with ...
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