Sunday, May 1, 2016

Individualized Rituxan?

The San Diego Union-Tribune published a very interesting article last week called "Individualized Lymphoma Therapy May Be Resurrected." I think the Tribune was especially interested in this because it involves work that was done years ago by a San Diego company. (And before I go any further, I have to thank Patients Against Lymphoma, who linked this article on their Facebook page.)

The article focuses on work by Dr. Ronald Levy from Stanford University, who was important in the development of Rituxan. Years before that, Dr. Levy was part of a project that developed a monoclonal antibody that was individualized for each patient.

If you've been reading for a long time, you know I've been fascinated by individualized treatments, like the vaccines that come around every once in a while (but still haven't quite taken off yet). They recognize that while a disease like Follicular Lymphoma is a certain disease with certain characteristics, every patient's will be just a little bit different. So a treatment that can deal with those little differences and target someone's own individual cancer situation would be very valuable.

Now consider Rituxan, the monoclonal antibody that changed everything -- making other treatments better and extending our lives.

Now bring them together. Sounds good, doesn't it?

A version of that treatment was put into trial in 1981, for 50 patients. One of those 50 went into remission for 32 years, and died at age 99, with no lymphoma. (Are you reading, Marie?) Of course, there's nothing in the article about the other 49 patients, but there was enough success to make it worth looking into again.

here's how it worked: Rituxan, as we know, targets a particular protein (CD20) on B cells, the immune cells that turn cancerous for us with FL. Rituxan targets ALL B cells, not just the cancery ones, so some people can have immune system issues for a while after they have Rituxan. (Not too severe -- it doesn't wipe out the entire immune system the way a Stem Cell Transplant would.)

If there was a way to make Rituxan focus only on cancer cells, that would be great. But that would involve the kind of individualization that can get very expensive.

That's where Dr. Levy and his team come in. By using something called a Peptibody, they can target individual cancer cells for each patient. Unlike some of the lymphoma vaccines, that depend of manipulating and then growing a patient's own immune cells to fight the cancer, the Peptibodies approach relies on a "library" of peptides, which are small sections of proteins. By going through the library and matching a peptide to the patient's individual cancer cells, and then attaching it to a Rituxan molecule, the Rituxan can more easily target the cancer.

Think of it this way -- I just heard a radio advertisement for a windshield replacement company that bragged about having 160,000 windshields in their warehouse. So we'll go with that comparison.

Imagine you broke your car's windshield, and needed a replacement. You could call Joseph's Artisan Windshields, and Joe would come to your house, measure your car, and go back to his artisan studio, where he would melt some glass in his furnace and with a large tube, blow and shape a windshield that fits your car perfectly, because it was made only for your individual car. It will account for that bump near the roof where your kid's baseball hit it, and that dip from where the moulding melted when your other nerdy kid left a magnifying glass there. Perfect fit. Of course, that perfect fit from the artisan shop took 5 weeks and cost you $6000. (And your insurance company wouldn't pay for it.)

That's the individualized vaccines that have been developed in the past. They might work well, because they are made just for you. But they take a long time and are very expensive to create.

Now imagine that instead, you call Joey's Glass Replacement. You give them the make and model and year of your car, they go to their warehouse of 160,000 replacement windshields, and they find the one that is probably going to fit. They add a little extra moulding and bump up the dent, and they make it fit. It's doe in 2 hours, not 5 weeks, and it costs $200. They're cheap because they aren't made one at a time in a glass blowing studio, but in a factory that churns them out by the hundreds.

And that, of course, is the new model. Instead of making it exactly to your car (or cancer), it goes through a bunch that are already made and finds the one that is most likely to work. It will still be individualized to you and your cancer (nobody is going to try to put a big Escalade windshield on your little Fiat), but not quite as individualized as the older model. And unlike the older vaccine model, which had to wait for live cells to grow, the peptides are chains of proteins that can be made quickly and cheaply by chemical means.

The peptide/Rituxan combo kills cancer cells on its own, but also helps immune cells called macrophages eat up those cancer cells, too.

So what you end up with is the effectiveness of Rituxan with the individualization of a vaccine.

The trick here is going to make it work well enough to justify the cost, even if the cost would be a lot less than a vaccine. Rituxan is already pretty inexpensive, compared to a lot of other treatments, given how effective it is, and its patent is expiring soon, so generic versions will be even more inexpensive. Trials will have to show that the extra cost of adding peptides will be worth it because it will work even better than Rituxan on its own (or better than standard chemos, or other newer treatments).

It's possible that this could come to clinical trials in a year. we'll have to see. A better version of Rituxan has been hard to find. Maybe this will be the one? If you're going to bet on someone, Dr. Ronald Levy is a true Lymphoma Rock Star -- could be a pretty good bet.

(Read that Tribune article. Links to  Dr. Levy's lab study results, and a podcast in which he talks about the treatment.)

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