Journal for immunotherapy of cancer
Development and preclinical evaluation of tetraspecific antibodies in combination with ex vivo expanded NK cells infusion for improved control of esophageal cancer
By Liu Y, Fan X, Zuo X and 7 others.
Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous, leading to limited drug effectiveness and resistance. Antibody therapies offer limited benefits due to low response rates. Multispecific antibodies, targeting multiple tumor antigens and natural killer (NK)-cell receptors, may overcome these challenges, but their effectiveness in ESCC therapy is not yet understood.
Methods
Transcriptome sequencing and database analysis were performed on samples from patients with ESCC to identify tumor antigens. Multispecific antibodies were designed to target tumor antigens and NK-cell surface markers. Fast protein liquid chromatography and surface plasmon resonance were applied for quality control of antibodies. Using multiple ESCC cell lines and NK cells from different donors, flow cytometry was performed to assess NK cell cytotoxicity and activation. Immunofluorescence assays were used to confirm colocalization. Transcriptome sequencing, flow cytometry and western blots were performed to explore molecular mechanisms. Subcutaneous and metastatic xenograft tumor models were established to evaluate the in vivo antitumor efficacy of antibodies combined with adoptive transfer of NK cells.