Monoclonal antibodies against cancer can very specifically recognize antigens on cancer cells and activate the immune system against them. These agents have previously shown improved therapeutic effects in various cancer types. All these antibodies are of the IgG isotype. We have learned that antibodies of the IgA isotype are able to activate the most common white blood cells of the human body against cancer better than IgG antibodies. In our latest KWF project we learned that IgA antibodies need a relatively large amount of antigen to kill the cancer cell.
Research direction/proposed solution
We would like to create a new type of IgA antibody in the lab, which will allow twice as many antibodies to bind per cancer cell. This also allows twice as many immune cells to be bound/activated per cancer cell, so that they can be killed more efficiently
Relevance
If our new IgA can bind twice as much antibody to the tumor, patients with low antigen expression can also be treated with antibodies of the IgA isotype.
Research questions
Can we develop a new IgA antibody in the lab? Do the new IgA antibodies indeed bind more to cancer cells than the regular IgA antibodies? Do the new IgA antibodies kill cancer cells better than the regular IgA antibodies?
Research design
The new antibodies will be produced by a new technique (‘protrusion in hole’ or ‘knob-into-hole’ technique). These antibodies were then purified and tested for binding to cancer cells and killing these cells. This is indeed strongly increased as we show in our preliminary data, both in the test tube and in a preclinical model. In the current project proposal we want to show that the improved IgA will also work well in a long-term tumor model. In addition, tumor tissue from patients will be used to evaluate whether these antibodies also work on this material.
Expected outcomes
We have already produced and purified the new IgA antibodies and have seen that they indeed bind to tumor cells with more molecules and that they can kill tumor cells better in the test tube and in a short mouse model. Now we also want to prove this in a long tumor model, so that we can better support our patent application. On the advice of the patent attorney, we will also show a Proof-of-Concept for a new target that occurs on lymphoma in children.
Description of steps needed to implement results
If we can indeed show in this project that the new IgA antibody works better and will therefore work better in cancer patients and we have protected this in a patent, we will approach commercial parties to take this idea further to the clinic. If further tests show that the drug is effective and safe, the antibody can be produced for testing in humans. If the drug also proves to be safe and effective in humans, this drug may become available for use for the relevant cancer types.
2023-11-22 01:14:36
#IgA #antibodies #treatment #cancer
