The emerging
chimeric antigen receptor (CAR) T cell revolutionized the clinic treatment of hematological
cancers, but meet its Waterloo in solid
tumor therapy. Although there exist many reasons for this limitation, one of the largest challenges is the scarcity of recognition for
tumor cells, resulting in the undesirable side effects and the subsequent ineffectiveness. To overcome it, a
lung-cancer-cell-targeting
peptide termed A1 was used in this work to reform the scFv domain of CAR by genetic manipulation. As a result, this modified A1CAR T exhibited the optimized
cancer-cell targeting and cytotoxicity in vitro and in vivo. More importantly, by tuning the sensitivity of CAR to
antigen,
peptide-based A1CAR T cells could distinguish
tumors from normal tissue, thereby eliminating the off-
tumor toxicity in healthy organs. Collectively, we herein constructed a genetic
peptide-engineered CAR T cells by inserting A1
peptide into the scFv domain. Profitted from the optimized recognition pattern and sensitivity, A1CAR T cells showed the ascendancy in solid
tumor treatment. Our findings demonstrate that
peptide-based CAR T holds great potential in solid
tumor therapy due to an excellent targeting ability towards
tumor cells.