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A project log for Personalized medicine

A website where oncologists can upload their patients' HLA types. They receive a list of peptides that may be used as a vaccine.

Jean Pierre Le RouzicJean Pierre Le Rouzic 11/08/2017 at 08:150 Comments

There are many web services that tell which peptide fits the best to a HLA type.

Indeed the first step in creating a personalized vaccine should be to choose the peptide that will trigger a response by the immune system.

* One problem is that there is nothing as "a response by the immune system":
        Because there are several immune systems.

* Another is that there is nothing as "triggering a response".
        The same peptide could trigger an immune response against cancer cells, but it could actually trigger a response that promotes cancer.

* The immune system has mechanisms to block unwanted immune responses, the famous "check points" that stopped cancer immunology to progress during decades. True there are "check point inhibitor" drugs, but using them is playing with fire.

* HLA typing is not even close to being "personalized". HLA typing as done by the industry, will search for less than 10 major HLA types.
        HLA types are personal, they are "genetically highly variable" and it is what makes each of us different from the next person. We evolved this way in order to make spreading of a contagious disease difficult.

* Cancer is a tissue disease, before being a genetic disease. Something that inhibited cancer immunology for a long time was the fact that the immune system could not penetrate inside tumors (for complicated reasons).

* Even if we can find the best peptide, there will be lots of side effects. Current web services give a molecular answer to the question, not a medical one. Actually they answer to the question: "Which peptide docks the best on a conventional HLA type". There is nothing about the patient and her side effects. Side effects could kill the patient quicker than her cancer.

* Molecular docking is an insolvable problem when using classical computation. Maybe quantum computers will change that, but for now there is no quantum computers. So how work those web services? It is simple, they train a Machine Learning algorithm (the kind we use in our Heart Failure detector) and the algorithm can easily spit out some answer. Each academic that wrote such a service dismiss other proposals, but is unable to prove that her ML algorithm is better. ML is a dirty process that should be used for things that are not vital, or things that could be crossed checked many times. While this is what could be called "an educated guess", it is unethical to use it to create a vaccine.

* If you want to have an immunology targeted treatment, you have to convince your doctor. It will be impossible to discuss with her if there is not a medical or scientific article that mention how this peptide could be useful for that kind of cancer. As far I know there is no peptide/HLA docking web service that do that.