Reinvigorating the Immune System to Attack Cancer Cells Using Highly Specific Antibodies
Cancer immunotherapy targets the tumor microenvironment, blocking the molecular pathways that tumors exploit to prevent immune cell activity.
Bijan Etemad-Gilbertson has over twenty-two years of industry experience working on antibody therapeutics for cancer at both small and large biotech companies. His expertise in manufacturing and translating antibody therapies together with his passion for scientific inquiry, drug discovery, applied therapeutics, and molecular biology drive his motivation to bring cutting-edge treatments to the clinic. In his current position as head of antibody technology at NextPoint Therapeutics, Etemad-Gilbertson leads unique research and development programs that leverage the immune system’s intrinsic capacity to eradicate cancer cells.
What is the focus of NextPoint Therapeutics’ innovation?
NextPoint Therapeutics is centered around a novel checkpoint axis using targeted molecules that reinvigorate the immune system to attack cancer cells. There has been a lot of success recently with PD-1, PD-L1, and CTLA-4 antibodies, which are safer and better tolerated than chemotherapy or radiation. These antibodies enter the tumor microenvironment and block immune checkpoints—proteins that normally prevent immune cells from attacking healthy cells and that tumors leverage to turn off T cell and NK cell activity. We're blocking or de-repressing these pathways.
At NextPoint, we're working on a novel pathway based on the findings of some of our founders. We're making antibody therapeutics that are highly specific to checkpoint molecules in the novel axis. We're hoping to file an Investigational New Drug application with the FDA in the first quarter of next year. As part of that we have to generate a lot of assays to support the preclinical and clinical analysis. We are also generating an anti-drug activity assay to detect whether the patient's immune system makes antibodies against our molecule, which would be detrimental to the success of our drug because the immune system would clear the antibody and prevent it from working.
How are you partnering with Fortis to advance this work?
We outsource a lot of our work through CROs—there are only twelve of us in the company and even though we're only three years old, we already have a huge pipeline. We engaged with Fortis for their rabbit antibody campaign. Immunoglobulins are highly concentrated in the circulation. If an antibody is not very specific, it ends up binding a lot of things. We sent them our antibody of interest and an isotype control, which is an antibody that is exactly the same as ours except in the binding site. They immunize rabbits with our molecule, collect the B cells—which produce a very specific rabbit antibody—and screen that antibody to make sure it recognizes our molecule. They also counter screen to make sure that the positive rabbit antibody does not bind to the negative isotype control. That's a great way of finding an antibody that is incredibly specific to our drug.
This is a standard procedure with the right molecule and the right negative control. However, some molecules are not antigenic. For example, immunizing a rabbit with a molecule that is very similar to one they have previously seen may lead to tolerance and failure to generate a large immune response, in which case there may be poor antibody yield. In the past, I mostly worked with mouse monoclonal antibodies, so it was nice to see high yields with Fortis’ rabbit campaign. The process was very easy because they had already cloned each B cell, so they could go back to them and then produce more antibodies to increase yields.
What are the next steps for this project?
We're going to take the lead antibodies and develop companion diagnostics. This entails working with a company that has GLP and GMP facilities, which enables sending a kit to a clinical site that is ready to use.
