Gene Editing Platform
Novel CAR-T technologies targeting solid tumors:
- Antibody engineering
- Expression technology
- Gene editing
Autologous T cells engineered to express chimeric antigen receptor (CAR) against the tumor specific antigen have proved to be highly effective in treating many cancers, especially in B-ALL and NHL. However, these therapeutic cells have to be custom-made. It is difficult and expensive to manufacture for patients who do not have sufficient healthy T cells, especially in infants or heavily treated patients. On the other hand, allogenic CAR-T cell therapy is limited because of potential rejection of the engineered donor cells by recipient.
By applying lentiviral technology with CRISPR/cas9-mediated cell engineering to generate universal CAR-T cells (UCAR-T) from non-human leukocyte antigen (HLA)-matched healthy donor cells. The UCAR-T cells could evade host immunity in unmatched patients and deliver anti-tumor effects with controlled risk of graft-versus-host disease (GVHD).
Although recent-developed gene editing tools have significantly improve the capacity for genome modification, CRISPR/Cas9 technology has revolutionized genome editing. CRISPR/Cas9 system has been broadly applied to edit genomes. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the double strand can be broken at a specific location, allowing disrupting the gene of interest.