Monoclonal antibodies (mAb) facilitate the recognition of cancer cells by the Natural Killer (NK) cells and trigger antibody-dependent cell cytotoxicity (ADCC). While the Fab region of an antibody binds to cancer cell antigens with high affinity/specificity, it's Fc region binds the CD16a receptors on NK cells with low affinity/specificity (Fig. 1A). This low affinity/specificity not only restricts the ADCC of mAbs but also inhibits B cell maturation and macrophage activation. As a result, the immune system’s response to cancer cells remains significantly suboptimal. While the race is on to address this deficiency, at present, there is no mAb in the market that can bind to CD16a receptors on NK cells with high affinity and specificity.
Rutgers scientists have developed a novel small size (~32 kDa) bispecific natural killer cell engager (BiKE) with high affinity/specificity towards CD16a receptor on NK cells and HER2 antigen on cancer cells (Fig. 1B). The BiKE was constructed by recombinant fusion of an anti-CD16a VHH with an anti-HER2 VHH. Since the developed BiKE targets HER2 antigen it may have application in the treatment of HER2+ breast, lung, liver, ovarian, pancreas, and gastric cancer. The flow cytometry, ELISA, and BLI data have confirmed the high affinity and specificity of the BiKE. In addition, the cell toxicity studies using HER2+ ovarian and breast cancer cells have demonstrated that the developed BiKE has significantly higher ADCC than the best-in-class FDA-approved anti-HER2 mAbs. The technology offers a promising approach for immunotherapy of HER2+ cancers.
- High affinity and specificity
- High stability and ease of large-scale production
- low toxicity and immunogenicity
- Superior efficacy to best-in-class mAbs
- Increased penetration and diffusion in tumors
- Cancer Immunotherapy
- Tumor imaging and phenotyping
- Targeted radiotherapy
Intellectual Property & Development Status: Patent pending. Available for licensing and/or research collaboration.
TTO Home Page: https://techfinder.rutgers.edu
Name: Shemaila Sultana
Title: Assistant Director