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. GM-CSF (Granulocyte-macrophage colony-stimulating factor), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The GM-CSF receptor consists of an α chain and a β chain, which bind GM-CSF with low and high affinity, respectively, and the β chain is shared with the IL-3 and IL-5 receptors. The GM-CSF receptor (CSF2R) is present on myeloid cells and some non-hematopoietic cells, but is not expressed by lymphocytes such as T cells. Through CSF2R, GM-CSF triggers multiple signaling pathways, including phosphatidylinositol 3-kinase (PI3K), JAK/STAT, and ERK1/2 signaling. Due to the important role of GM-CSF as a colony-stimulating factor, GM-CSF has been used clinically to restore the bone marrow cell population of leukemia patients after chemotherapy/radiotherapy. In addition, GM-CSF is also involved in innate and adaptive immunity. Targeting GM-CSF may represent a novel approach to control adverse immune responses in autoimmune diseases and chronic inflammation. This product is designed as a tool for the delivery and expression of anti-HER2 CAR-GM-CSF mRNA for research. The product leverages the lipid nanoparticle (LNP) technology platform for simple and efficient delivery of anti-HER2 CAR-GM-CSF 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-GM-CSF in this product is approximately 75 kD and consists of anti-HER2 CAR and GM-CSF (144 amino acids, GenPept accession number: NP_000749) 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-GM-CSF mRNA-LNP product is available upon request.
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