Provided in the present invention is a
T cell receptor engineering modification method, which comprises the steps of: obtaining CDR regions of a given
T cell receptor sequence by means of a
database, mutating one or more
amino acid residues in the CDR regions into
histidine, and establishing a first
T cell receptor mutation library. The T
cell receptor
engineering modification method provided by the present invention is based on a
histidine scanning method, realizes TCR
engineering modification independent of three-dimensional structures, overcomes the disadvantages of high affinity and realizes the modification of TCRs with
low affinity and
high activation, thereby providing more options for clinical use. The T
cell receptor provided by the present invention comprises the following six CDR regions, CDR1α, CDR2α and CDR3α in a TCRα chain, and CDR1β, CDR2β and CDR3β in a TCRβ chain, the
amino acid sequences of which are shown as SEQ ID No. 1-6, respectively. In the present invention, engineering modification of a wild-type MAGE-A3 TCR molecule is achieved by means of a catch bond to obtain an efficient and non-toxic TCR targeting MAGE-A3, which is free of toxic and side effects caused by
affinity maturation. Moreover, the engineered TCR is applied to TCR-T
cell preparation for
solid tumor treatment.