Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy

Immunosurveillance NKG2D HLA-B Targeted Therapy
DOI: 10.1016/j.heliyon.2024.e35697 Publication Date: 2024-08-03T03:04:29Z
ABSTRACT
Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness existing therapies limited. Immunotherapy a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands NK cells. Shedding MICA/B from surface tumor cells by cleavage at membrane proxial region in α3 structural domain immune evasion strategies leading to escape immunosurveillance. In this study, we generated panel monoclonal antibodies (mAbs) identified mAbs, mAb RDM028, that had high binding affinity recognized site on critically important MICA/B. Our study has further demonstrated RDM028 augmented expression HCT-116 human CC inhibiting shedding resulting enhanced cyotoxicity against mediated anti-tumor activity nude mouse model colon cancer. These results indicate could be explored developing as an effective immuno therapy targeting promot immunosurveillance MICA/B-NKG2D interaction.
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