Herceptin is an FDA-approved antibody targeting HER2, a protein expressed on many tumor types. The occurrence of acquired resistance, in which tumors find alternate signaling pathways thereby ending their “addiction” to HER2 activation, is a common problem for HER2+ breast cancer patients treated with Herceptin, and it renders Herceptin treatment ineffective. To address this problem, inventors at Memorial Sloan Kettering have generated a highly effective antibody construct that recognizes both HER2 and CD3, a protein expressed on T-cells.
This bispecific antibody construct combines the proven tumor-targeting ability of Herceptin with the ability to recruit T-cells to the tumor which can then kill the tumor. Data from mouse models has shown that this new bispecific HER2xCD3 antibody construct is more effective in killing tumor cells than Herceptin alone and can virtually eradicate human tumor grafts.
This technology can overcome several limitations of regular Herceptin therapy:
- It works in Herceptin-resistant tumor models
- It kills tumor cells with higher efficiency
- It requires much lower HER2-expression levels on the tumor cell to be effective
- It can engage any T-cell of a patient, as opposed to only those that are tumor-specific
HER2 is expressed in a wide variety of solid tumors, including breast, gastric, osteosarcoma, and head-and-neck cancer, making this an important therapeutic target. As indications of potential market size, Herceptin sales in 2013 amounted to $6.8 billion, while those of Perjeta were about $300 million. Kadcylca sales for 2014 are estimated at roughly $600 million.
Preparation for large scale production of the bispecific antibody and IND-enabling animal studies are under way.
PCT application PCT/US2015/041989 filed in July 2015
Nai-Kong Cheung, MD, PhD, Laboratory Head, Memorial Hospital Research Laboratories; Enid A. Haupt Chair in Pediatric Oncology, Memorial Sloan Kettering