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April 3, 2007
Vaccines Everywhere
Posted by Derek
You know, small-molecule folks like me are going to have to learn to deal with immunology. I don't mind saying that it's not my field - yet - but who knows, perhaps it will be. The recent successes of Dendreon and (today) Cell Genesys prompt these thoughts. Both companies have shown useful efficacy with immune-based prostate cancer therapies, good enough to make you wonder how effective these things will eventually be when we understand more about what's going on.
As things stand, there are a bewildering number of possibilities. Both of these vaccines depend on production of GM-CSF secreting cells (a powerful cytokine which stimulates white blood cell production and activity), but they're rather different otherwise. Dendreon's Provenge is autologous, that is, derived from each patient's own cells, for one thing, while the Cell Genesys GVAX vaccine isn't individualized at all (that is, allogeneic). That's just the first choice to make. There are all sorts of options about what kinds of cells to use, which antigens to decorate them with and what proteins to have them secrete, how to administer them to patients singly and in combination with other conventional chemotherapies, and so on. This work has been going on for years now, and I've no doubt that a lot of blind alleys have been followed. And a lot more will get followed, too, but the results so far are pretty impressive. They're beating the small-molecule conventional therapies in the difficult cases, that much is clear. It's important to remember that the patients are still dying of cancer, but they're taking noticeably longer to do it, which is success in our era.
We'll probably see a rush into the stocks of every company that has both "cancer" and "vaccine" in its 10-K filings, but I'd say be careful. For example, if you bought Cell Genesys last week, you're quite happy. But if you bought it this time last year, you're still in the red. Although I find these current results quite interesting, the field is still very young indeed. Companies are targeting prostate cancer because it's a non-essential organ (so it doesn't matter if the immune system trashes it), but they're also going to be going after tumors in rather more vital organs like the lung and pancreas. Development of immune therapies in those areas is going to be full of more excitement than some of the stockholders will be ready for.
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1. TotallyMedicinal on April 4, 2007 2:17 AM writes...
Medarex have an antibody (ipilimumab) in Phase 3 (with BMS) targeting melanoma. It is based on antibody inactivation of an immune-response suppressing antigen (CTLA-4), which has thus far shown encouraging results. As you say, there is the potential for the immune system to go into overkill mode, but thus far the side-effect profile noted for ipilimumab has not been too appalling (and those patients who have the severest side effects also respond best to the therapy). Obviously there is the potential for things to go TeGenero wrong.
GVAX is undergoing a combo trial with ipilimumab, and I reckon that these combinations of vaccines (whether autologous or not) and antibodies have a lot of promise.
PFE also have an anti-CTLA4 antibody in Phase 3 (ticilimumab), but I know less about that one (not a PFE shareholder)
BMS have other programs in the immunotherapy based oncology area on CD147 (if I remember correctly), and Medarex on PD-1 (although these are much earlier stage). A Medarex spin-out Celldex in another immunotherapy based company (their clinical focus is currently on glioblastoma).
A very exciting field!
Note: I am a Medarex shareholder
Permalink to Comment2. Brian at babybiotechs.com on April 4, 2007 12:44 PM writes...
I'm not an immunologist either, but I do know that cancer cells are highly mutable. Mutations in the protein(s) expressed as an antigen by the cancer cell to the immune cells will render these therapies ineffective. They're not going to cure cancer, but as you say, prolonging life is better than nothing.
Permalink to Comment3. Cockroach on April 4, 2007 2:12 PM writes...
"prolonging life is better than nothing"
You really believe that line. Most of my friends who have struggled with cancer gained only weeks or months of bedridden torment... amplified by side-effects and a knawing disease that renders one a lifeless existence... hardly, better than nothing...
But we have to keep hopes alive, right?
Permalink to Comment4. Smoki on April 5, 2007 7:40 AM writes...
"Mutations in the protein(s) expressed as an antigen by the cancer cell to the immune cells will render these therapies ineffective."
Certainly, but high mutation rate represents an obstacle for all cancer treatment strategies. Combining different therapy methods will therefore probably (still) be the best approach for treating cancer patients.
But the mutations of cancer cell antigens might be the key feature that will enable immunotherapy in the first place. A big problem with attacking cancer cells lies in the fact that they are our own cells gone bad - so they basically present the same antigens as many other normal cells in the body. Devising therapy for cancers of essential organs will therefore be very hard - you wouldn't want your immune system to start attacking the normal cells in your lungs, for example. One option would perhaps be to target the mutated antigens, that are different from those presented on normal cells. But this would probably require individual-based approach, and I think we're still a long way from that.
This is all pretty much theoretical, I don't know if it makes sense from the pharma point-of-view.
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