Bispecific chimeric antigen receptor based on variable domains of heavy chain of heavy-chain antibody and application thereof
2015
The invention discloses a bispecific chimeric antigen receptor based on variable domains of a heavy chain of a heavy-chain antibody and an application thereof. The bispecific chimeric antigen receptor based on the variable domains of the heavy chain of the heavy-chain antibody is composed of CD8 signal peptide, the CD19 antigen-specificity variable domain of the heavy chain of the heavy-chain antibody, the CD20 antigen-specificity variable domain of the heavy chain of the heavy-chain antibody, a CD28 transmembrane domain, a CD28 intracellular signal transduction structural domain and a CD3 intracellular signal transduction structural domain in a sequential series connection mode. According to the bispecific chimeric antigen receptor and the application, as the design of the CD19 antigen-specificity variable domain of the heavy chain of the heavy-chain antibody and the design of the CD20 antigen-specificity variable domain of the heavy chain of the heavy-chain antibody are optimized, a CD19 and CD20 double-target-spot modification CAR-T cell is provided and can be specifically combined with a CD19 antigen and a CD20 antigen. In a B lymphocyte cell line malignant tumor killing test, compared with single CD19 or CD20 CAR-T, the method that a CAR-T therapy is implemented through the CD19 and CD20 double-target-spot modification CAR-T cell has the advantages that the tumor cell target identification capacity of an immune cell is obviously improved, and the tumor cell killing activity is also improved.
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