Noncanonical amino acid-aided synthesis of anti-PD-L1 bispecific nanobody for colon cancer immunotherapy.

ABSTRACT: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality, and the incidence of early-onset colon cancer has been increasing globally in recent years. The development of immunotherapies for colon cancer is critical for providing new treatment strategies to combat drug resistance. Here, a bispecific nanobody against PD-L1 (BsNb-PD-L1) constructed using genetically encoded noncanonical amino acids (ncAAs) is reported. A computational protocol was developed to identify appropriate sites in the nanobody for incorporating p-acetylphenylalanine (pAcF). Variants of nanobodies PV2 and PV3 with pAcF incorporated were conjugated with linkers containing an aminooxy functionality to enable oxime ligation. The resulting PV2-S71 + PV3-N77 bispecific nanobody (BsNb-ncAA) exhibited h

SUBMITTER: Hu X 

PROVIDER: S-EPMC12749753 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature