Anti-Her-2 CAR/CCL2 mRNA-LNP

HER2 (human epidermal growth factor receptor 2) is a member of the human epidermal growth factor receptor (ERBB) family and is encoded by the human ERBB2 gene. In contrast to other members of the ERBB family, HER2 does not directly bind ligands. HER2 is overexpressed in a range of tumors, including breast, gastric, lung and ovarian cancers. It can be activated by heterodimerization with another ERBB member or by homodimerization when HER2 concentrations are high, such as in cancer. Overexpression of this oncogene has been shown to be associated with the development and progression of certain aggressive types of breast cancer. Therefore, HER2 is an important target for cancer therapy.
CCL2 (Chemokine (C-C motif) ligand 2), commonly known as monocyte chemoattractant protein-1 (MCP-1), belongs to a family of secreted proteins involved in immune regulatory and inflammatory processes. Mature wild-type CCL2 protein has a full length of 76 amino acids, and its N-terminal residues are crucial in activating the CCL2 signaling pathway. The CCL2 mutant (9-76 amino acids), also known as 7ND, is a deletion of the first 8 residues of wild-type CCL2, which can bind to the C-C chemokine receptors CCR2 and CCR4 on the surface of monocytes, but cannot activate the down-regulated pathway. Therefore, the CCL2 mutant can be used as an inhibitory form of wild-type CCL2 to block the C-C chemokine receptors of CCL2 and inhibit unwanted monocyte/macrophage recruitment.
This product is designed as a tool for the delivery and expression of anti-HER2 CAR-CCL2 mRNA for research. The product leverages the lipid nanoparticle (LNP) technology platform for simple and efficient delivery of anti-HER2 CAR-CCL2 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-HER2 CAR-CCL2 in this product is approximately 65 kD and consists of anti-HER2 CAR and CCL2 (76 amino acids, GenPept accession number: NP_002973) with a GS linker (15 amino acids) in between. The anti-HER2 CAR contains scFv (single-chain variable fragment) linked to a second-generation CAR (chimeric antigen receptor) containing the CD8 hinge and transmembrane domain and 4-1BB and CD3ζ signaling domains. The full-length amino acid sequence of this anti-HER2 CAR-CCL2 mRNA-LNP product is available upon request.