Posted on July 16th, 2015
by David Hansen
The term “fully human antibody” is a misleading term. Many assume that it means that the antibody was physically taken from a human. Technically, it only means that the antibody has been created from entirely human genes, but not necessarily rescued from an actual person.
Today’s “fully human” antibodies are actually harvested from something called a phage display (viruses that infect bacteria). Human antibody genes are stuck into a phage, which then displays the antibodies on its surface. These are tested for reactivity with an antigen, and the “best ones” are harvested and replicated. I put “best ones” in quotations because while the resulting antibodies bind to the selected target there is little way of knowing which antibodies coming out of a phage will be effective, since they have never been seen by the human immune system before being harvested from the phage. Scientists can take educated guesses by which ones lock on to an antigen target, but locking on does not necessarily mean it will be a good therapeutic. If it did, getting monoclonal antibodies approved and to market would be a cinch.
MabVax’s antibody discovery platform works much differently. We are the only company in the world that really does find fully human antibodies in the full sense of the term. We have licensed 8 different cancer vaccines from Memorial Sloan Kettering Cancer Center. These vaccines are constructed to raise an antibody response against key cancer targets, antigens, that are expressed on certain solid tumors. Real human patients produce real fully human antibodies in response to these vaccines and that is the source of our beginning discovery material.
One of the main strengths of cancer vaccines is that the body produces many different antibodies in response to them, some of which are much more effective than others. Two patients responding to the same vaccine can produce entirely different sets of antibodies. In addition, the vaccine treatment regimen vaccinates patients multiple times over a short period of time. Each vaccination drives a more effective antibody response because the human immune system continues to build upon and improve upon each earlier response. While this process produces many antibody candidates, once these antibodies are filtered by our discovery platform, we can pinpoint the ones that work the best regardless of which patient the “ideal” antibody comes from. The best antibody becomes the potential product for all patients who may have the same disease. We continue to confirm our choice by evaluating each antibody in action against cancer cells in a human therapeutic context.
Ours is the only antibody discovery platform in existence today where picking the right antibody is much less of a guessing game. Since we vaccinate patients with known antigens and then screen the resulting antibodies against the same antigens, our discovery process is highly directive. In a sense we are able to find the right antibodies because we know what we are looking for. Our lead antibody candidate discovered through this platform – our HuMab 5B1 – has already been seen in action in human patients, rather than just in vitro from a phage display.
The other major problem that the MabVax antibody discovery platform hopes to solve is unwanted side effects. Just because an antibody is built from human genes does not mean that it would ever be coded for in a natural or vaccine setting. When harvesting an antibody from a phage display, side effects could be problematic, because no one knows what other actions the antibody can have in the context of a human body.
There are currently only four fully human antibodies on the market against cancer. They all have serious side effects associated with them. There is a lower chance that any of our antibodies, including 5B1, would result in any serious side effects, because they have already been seen by the human body.
Finally, our unique platform opens us up to a myriad of partnership opportunities for the future, one of which is already in motion. Juno Therapeutics, which just got a $1 billion investment from pharma giant Celgene, is a pioneer in chimeric antigen receptor T cells, (CAR T cells) which are immune cells with specially tailored receptors on their cell membranes. These receptors are specifically designed to lock on to cancers, enabling the immune cell to recognize and attack the cancer. Our partnership with Juno gives them the option to use two sets of our antibodies as the targeting sequence for new CAR T cells targeting solid tumors.
Since we are the only company that harvests cancer antibodies directly from humans, it is very possible that Juno will not be the only multibillion dollar company we partner with, especially if our antibodies are successfully integrated into one of their products.
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