New FDA Approval looks really good!

Evarista said:

Excellent news

Particularly for those of us who are not candidates for the currently approved CAR-T cells that target CD19 and/or CD22.  Here's the FDA synopsis: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-diffuse-large-b-cell-lymphoma 

Be aware that while it sounds like a CAR-T, it seems (to me) to be an engineered antibody instead (like rituximab). Haven't dug into the details yet though.

Thanks for sharing, Bill

....mab

I have not even opened the link yet, but the fact that the drug ends in the ubitquious '....mab" seems to confirm Evarista correct: It is apparantly a new 'monoclonal antibody (hence the ending '...mab').  [Polatuzumab]

But, that is a good thing.  New drugs are comparatively cheap, regardless of per infusion price, compared to the million dollars  (~~) required for CAR-T, which remains a very dangerous proceedure in addition.

This drug may have been mentioned at the site I mentioned last week: Oncologygo.  I mentioned that nearly all of the Lymphoma-related presentations related to new developments against aggressive large-B NHLs, and follicular.

Nothing, anywhere, on what I had: NLPHL.      Nada, nicht !, null, ziltch.  But it makes sense that research is centered on the most common diseases; I get it.  I hope that these new drugs are effective, because the pattern is for new drugs approved for one thing to subsequently in later years being discovered effective against many others.  E.g., Bendamustine, Rituxan, etc.

 

ShadyGuy said:

Unfortunately ......

....... Polatuzumab is not a magic bullet. It attacks all b-cells, not just lymphoma cells. Its a long road and every step gets us closer to a cure so this is a really important development. Please note that the drug, as I understand it, uses human material unlike Rituximab which is made from Chinese Hamsters. Anybody who can verify this?

Human vs. hamster

Hi Shady, I have not delved into the specifics of rituximab production and it's backstory, but I believe that you may be crossing up "What it's made of" with "How it is made".  Completely understandable!  Most monoclonal antibodies used in clincial settings probably started their biochemical life as mouse antibodies.  They then got DNA engineered to be "humanized" to the extent possible. That bit is so that allergic reactions to them are minimized to the extent possible. But to produce the protein antibodies, mammalian cell cultures may be used.  The Chinese Hamster Ovary (CHO) cell line has been around for about umpteen years and is frequently used as just such a "production factory" for monoclonals. Other methods may be used as well.

Again: working from memory here, so please do not quote me! I find that I have difficulty processing technical literature these days, so I may not get to looking up more precise information...Sorry.

You might find this article interesting.  Production process schematic in Figure 5, but as noted in the paragraph above it, the process is proprietary:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994406/

ShadyGuy said:

Polatuzumab

Hi Evarista

poor choice of words on my part. Rituximab is just an antibody, primarily derived from Hamster DNA while Polatuzumab is a drug/antibody conjugate with the antibody portion designed primarily from human DNA. True both have hamster DNA but the Polatuzumab is largely “humanized”. The monocloning process which reproduces this “design“ for mass production I do not know much about.

does this hypothesis ring true?

The theory on all these drugs seems to boil down to one hypothesis - healthy b-cells are produced only in the bone marrow while lymphoma b-cells clone themselves insitu, wherever they happen to be.  T-cells are different story.  All b-cell lymphoma clones are mature b-cells. So, in very simplistic terms, the goal appears to be to kill all mature b-cells everywhere in the body. After that the bone marrow hopefully continues to produce healthy new b-cells to replace them. If new cells from the marrow are healthy, why did my marrow test as containing 26% lymphoma cells? The tentative answer is that blood circulates through the bone marrow and brings diseased b-cell clones with it. They clone themselves wherever they happen to be, including in the bone marrow. A big issue and hope for the future is to find a treatment that kills only b-cell clones and not healthy b-cells. The so-called “magic bullet”. This has proven to be a very elusive goal.The best hope seems to be an agent which chemically interferes with the cloning process, thus preventing new cancer cells from being cloned.

Please comment if I have this wrong.Its an important concept for all of us. I realize the issue is much more complex than this simplistic explanation. The devil is always in the details.