Technology Bundle ID
NCI-E-351-2013

Her2 Monoclonal Antibodies, Antibody Drug Conjugates as Cancer Therapeutics

Applications
Therapeutics
Lead Inventors
Dimiter Dimitrov (NCI)
Co-Inventors
Boopathy Ramakrishnan (NCI)
Pradman Qasba (NCI)
Zhongyu Zhu (NCI)
Development Status
Pre-clinical (in vivo)
ICs
NCI

Antibody drug conjugates (ADC) can demonstrate high efficacy as cancer therapeutics, however, much more can be done to improve their efficacy and safety profile. Site-specific antibody drug conjugation is a promising way to do this. Scientists at the NCI’s Laboratory of Experimental Immunology have identified a fully human monoclonal antibody, m860, that binds to cell surface-associated Her2 with affinity comparable to that of Trastuzumab (Herceptin) but to a different epitope. In addition, the scientist developed a site-specific glycan engineering method to conjugate the antibody to the small molecule drug auristatin F. The ADC prepared though this site-specific approach shows very good stability, cell surface binding activity and also potent specific cell killing activity against Her2 positive cancer cells, including Trastuzumab resistant breast cancer cells. This ADC has the potential to be developed as a targeted therapeutic for Her2-overexpressing cancers and this site-specific strategy could be readily applied to develop ADCs targeting other cancers that express cell surface markers or other disease targets.

Commercial Applications
  • Therapeutic for the treatment of Her2 positive cancers.
  • Method for producing safer and more effective ADCs.
Competitive Advantages
  • Could be used in combination with Trastuzumab or for patients who have developed resistance to Trastuzumab treatment, since this antibody targets a different epitope.
  • Site specific conjugation provides better efficacy and less side effects than ADCs produced using traditional strategies.
  • Can be readily applied to develop ADCs targeting other cancers that express cell surface markers or other disease targets, such as HIV.

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