anti-HLA-A*02:01/p53 R175H bispecific T-cell engager CLSP-1025

An asymmetric bispecific single-chain diabody (scDb) Fc fusion protein and T-cell engager (TCE) directed against the human TP53 (p53) R175H mutant peptide (p53(R175H)168-176) bound to human leukocyte antigen (HLA)-A*02:01 (HLA-A*02:01) and the T-cell-specific antigen CD3epsilon (CD3e), with potential immunostimulating and antineoplastic activities. Upon administration, anti-HLA-A*02:01/p53 R175H bispecific TCE CLSP-1025 specifically targets and binds to CD3 on cytotoxic T lymphocytes (CTLs) with its anti-CD3 domain and the p53(R175H)168-176 mutant peptide bound to HLA-A*02:01 expressed on tumor cells with its anti-peptide HLA (pHLA) domain. This activates and redirects CTLs to HLA-A*02:01/p53 R175H-expressing tumor cells, which results in the CTL-mediated cell death of these p53 R175H-expressing tumor cells. p53, a tumor suppressor gene, is mutated in many tumor cells, resulting in the loss of apoptosis regulation and abnormal cell proliferation.