The epidermal growth factor receptor (EGFR) is over-expressed in various human epithelial tumors usually due to the gene amplification. EGFR gene amplification in tumors frequently contain its rearrangements and among them, the most common extracellular domain mutation is receptor variant III, EGFRvIII (also known as de2-7EGFR or DEGFR). The molecular mass of EGFRvIII is approximately 145 kDa and this genetic change of tumor-specific mutation results from a deletion of 267 amino acids spanning exons 2-7 of the EGFR gene. These consequences make the variant EGFRvIII incapable of binding known ligand. It is expressed in a majority of patients with glioblastoma multiforme. And the evidence shows aberrant EGFRvIII signaling is important for driving tumor progression.
PD-1 or PDCD1 (Programmed cell death 1), also known as CD279, is a cell surface receptor expressed on T cells and pro-B cells, which was firstly isolated from a murine T cell hybridoma and a hematopoietic progenitor cell line in 1992. It is an inducible immune modulatory receptor and belongs to a member of the CD28 receptor family. The expression of PD-1 is significantly involved in programmed cell death of lymphocytes. PD-1 has two ligands that are PD-L1 (B7-H1 or CD274) and PD-L2 (B7-DC or CD273). Upon their interactions, PD-1 plays an active role in negative regulation of T cell responses to antigen stimulation and maintaining peripheral tolerance. Thus, it is regarded as an important immune checkpoint for therapeutic antibodies against cancers.