| abstract |
The present invention is directed to a nucleic acid sequence comprising: (a) a first polynucleotide encoding a chimeric antigen receptor (CAR) fusion protein comprising from the N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising V H and V L , wherein scFv specifically binds to a tumor antigen, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain; and (b) a second polynucleotide encoding an IL-6 short hairpin RNA (shRNA) sequence, or a check point inhibitor shRNA, wherein the check point inhibitor is PD-1, CTLA-4, TIM-3, TIGIT, or LAG-3. |