Anti-BCMA CAR-T2A-mbIL-15 mRNA-LNP
BCMA (B cell maturation antigen), also known as CD269, TNFRSF-17, is an ideal target antigen for novel multiple myeloma therapy due to its highly selective expression in malignant plasma cells. BCMA is a cell surface receptor of the TNF receptor superfamily that recognizes B cell activators and is encoded by the human TNFRSF17 gene. This receptor is preferentially expressed on mature B lymphocytes and is important for B cell development and autoimmune responses. This receptor has been shown to specifically bind tumor necrosis factor (ligand) superfamily member 13b (TNFSF13B/TALL-1/BAFF), thereby activating NF-κB and MAPK8/JNK. For targeting BCMA, chimeric antigen receptor (CAR)-modified T-cell therapy is one of the most common treatment modalities. Interleukin-15 (IL-15), encoded by the IL15 gene, is a member of the four α-helix bundle family of cytokines. Like IL-2, IL-15 binds to and signals through a complex consisting of the IL-2/IL-15 receptor beta chain (CD122) and common gamma chains (γ-C, CD132). IL-15 regulates the activation and proliferation of T cells and natural killer (NK) cells. As an inhibitor of the apoptotic pathway, IL-15 inhibits T lymphocyte apoptosis by inducing Bcl-2 and/or Bcl-xL. In preclinical models, IL-15 has been shown to enhance antitumor immunity of CD8+ T cells.
This product is designed as a tool for the delivery and expression of anti-BCMA scFv plus IL-15 TM-CYTO mRNA for research. The product leverages the lipid nanoparticle (LNP) technology platform for simple and efficient delivery of anti-BCMA scFv-T2A-IL-15 TM-CYTO mRNA to a variety of mammalian cells in vitro and in vivo. The LNPs used are formulated with SM-102, DSPC, cholesterol and DMG-PEG2000 at an optimal molar concentration for a high rate of encapsulation and efficient mRNA delivery. The anti-BCMA-T2A-IL-15 TM-CYTO in this product is approximately 70 kD and consists of anti-BCMA scFv and IL-15 TM-CYTO sequence with a T2A self-cleaving peptide (18 amino acids) in between, and the sequence is available upon request.