tag:blogger.com,1999:blog-14815894.post6919421728915894356..comments2024-03-27T06:52:45.545-04:00Comments on Bayblab: Tumor Immunology Is A Waste of TimeKamelhttp://www.blogger.com/profile/15548259062576527751noreply@blogger.comBlogger13125tag:blogger.com,1999:blog-14815894.post-45921223056889611582009-08-20T13:31:23.288-04:002009-08-20T13:31:23.288-04:00The clinical stuff is just correlation, am I right...<i>The clinical stuff is just correlation, am I right?</i><br /><br />Most of the trials are relatively small. I'm not sure if there are large-scale phase III trials ongoing. But the small-scale trials, done on people with cancers that have resisted treatment, have resulted in some spectacular cures. I don't really think there's any doubt that immune therapy of tumors has worked -- it's not mere coincidence when tumors that are invariably fatal abruptly disappear permanently after vaccination. It's very clear that tumor-induced immune suppression is not invariably insurmountable. <br /><br />As I say, it hasn't worked consistently, and immune suppression may be part of that. But even so, that doesn't mean it's an impossible problem. Apart from the fact that some cases have succeeed, it's at least theoretically possible to overcome immune supression. For example, the work with anti-CTLA4 and other ways of overcoming immune suppression is directed at exactly that. <br /><br />Arguing from the natural outcome of disease, that treatment is futile, is a fairly short-sighted approach. By that argument no treatment of any serious disease would ever be possible.iayorkhttp://www.iayork.com/MysteryRaysnoreply@blogger.comtag:blogger.com,1999:blog-14815894.post-51208901205998164212009-08-18T09:55:19.276-04:002009-08-18T09:55:19.276-04:00@iayork
I actually hadn't read that literature...@iayork<br />I actually hadn't read that literature before and the mouse model data is convincing that there is an adaptive immune component to tumour elimination. The clinical stuff is just correlation, am I right?<br />There is definitely an adaptive immune component to tumour rejection. We have seen this in our lab too (coincidentally(?) using the SAME mouse model as the nature med paper).<br />But does this argue that a cancer vaccine is a viable approach for treatment of naturally occurring human tumours? Is it not possible that the tumour microenvironment is much too immunosuppressive for such a strategy to have any chance at all? Again those crazy devil tumours suggest that tumour immune evasion can be pretty successful. <br />I don't read that kind of literature much, I probably should, so thanks for pointing it out.Robhttps://www.blogger.com/profile/11878582460269426199noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-29537628718555294742009-08-17T13:36:28.920-04:002009-08-17T13:36:28.920-04:00Which is a fair definition I suppose if we're ...<i>Which is a fair definition I suppose if we're talking about cancer therapy in general; chemo clearly is often successful but never ideal if the goal is to be specific in targeting disease.</i><br /><br />Interesting comparison. You probably know that several recent papers strongly suggest that chemo actually works by breaking tolerance, and it's not the chemo per se that eliminates the tumor, it's the immune response that's induced by the cell death. (See http://www.iayork.com/MysteryRays/index.php?s=chemo and especially http://www.iayork.com/MysteryRays/2009/02/24/more-chemotherapy-and-tumor-immunity/ for more, with references.)<br /><br />As I say, I don't think that tumors are non-antigenic. I think they have reduced antigenicity. It's a quantitative, not a qualititative, change, and so it needs a quantitative, not a qualitative change in immunization. I don't think it would be surprising that so far, the push is way too far; that doesn't mean that there's not a happier mean. <br /><br />The vitiligo associated with recponse to melanoma may be a special case -- not all tumor antigens are shared by normal cells. It's a complicated issue, of course.iayorkhttp://www.iayork.com/MysteryRays/noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-7954292857083989682009-08-16T23:47:59.755-04:002009-08-16T23:47:59.755-04:00The message from human clinical trials seems to be...<i>The message from human clinical trials seems to be that anti-tumor immunity works very well against some, perhaps even many, tumors, but not all;</i><br /><br />Ok, I can go along with that. This might describe some of the successes that have been achieved with Rosenberg-esque adoptive therapies for example. If you define success to mean "tumor regression at all costs". Which is a fair definition I suppose if we're talking about cancer therapy in general; chemo clearly is often successful but never ideal if the goal is to be specific in targeting disease.<br /><br />However my understanding is that success in clinical adoptive therapy correlates with the induction of autoimmune toxicities. Vitiligo in the case of melanoma and and lots of nastiness as the immune system is revved up to such an extent that nearly as much damage is exacted on healthy organs as tumors.<br /><br />To me, these kinds of results just support the notion that human tumors are just not antigenic. And that you cannot therefore vaccinate against cancer. A successful vaccination, like a flu shot, is not usually a near-death experience because it harnesses the specificity of the immune system in distinguishing self from non-self. You don't seem to have to crank up the immune system anywhere near the point of non-specific mayhem to get protective immunity to a virus or tissue rejection.<br /><br />I agree that anything that "works" is a step forward when we're talking about a deadly disease, and it's great that highly aggressive immunotherapy benefits a limited subset of patients.<br /><br />But I guess what I find lacking is evidence that the real idea behind cancer vaccines is a realistic goal, that it really is possible to harness the tremendous specificity of the immune system against cancer cells. But maybe my expectations are just too high.Baymanhttps://www.blogger.com/profile/03436172198266062229noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-29171265274638358202009-08-14T02:25:50.980-04:002009-08-14T02:25:50.980-04:00that picture hurts my heart.that picture hurts my heart.cnoreply@blogger.comtag:blogger.com,1999:blog-14815894.post-64067833918181625002009-08-13T23:28:47.078-04:002009-08-13T23:28:47.078-04:00I think the point of the post is there isn't m...<i>I think the point of the post is there isn't much evidence that it works. </i><br /><br />No, I disagree. There's tons of evidence that anti-tumor immunity works, and in fact there's tons of evidence that it works in therapeutic treatment of natural human tumors. What hasn't happened yet is <i>consistent</i> success, or even predictably inconsistent success. The message from human clinical trials seems to be that anti-tumor immunity works very well against some, perhaps even many, tumors, but not all; and we're not yet able to understand which are which.<br /><br />But that's a far cry from "not working".iayorkhttp://www.iayork.com/MysteryRaysnoreply@blogger.comtag:blogger.com,1999:blog-14815894.post-86384053252385769042009-08-13T21:18:22.467-04:002009-08-13T21:18:22.467-04:00@iayork
yeah, I understand the logic. I think the ...@iayork<br />yeah, I understand the logic. I think the point of the post is there isn't much evidence that it works. The devil tumours suggest that cancer can evade even the most fundamental aspects of immunological recognition.<br /><br />..."peaceful-looking, fairly cute" facing-ripping little guys..<br />I think there is a reason that they have a cancer that spreads through them biting each others faces!Robhttps://www.blogger.com/profile/11878582460269426199noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-10151652498523767632009-08-13T19:05:10.966-04:002009-08-13T19:05:10.966-04:00Rob:
I guess I'm suggesting something you alr...Rob: <br /><i>I guess I'm suggesting something you already know. Because these tumour cells have evolved to evade immunological rejection they may also lack the ability to recruit the immune system to fight off a virus infection.</i><br /><br />Tumor immune evasion (like viral immune evasion) isn't necessarily and all-or-none phenomenon. It isn't as if the tumor is 100% resistant, so you have to crank up the immune response by an infinite amount to control the tumor. If the immune system kills 99% of new cancer cells, the cancer may still end up growing rapidly enough for detection. But all you'd need to do is bump up the immune response by 2% and then you'd get it under control. <br /><br /><i>Too bad those things look like they would rip my face off.</i><br /><br />Most popular pictures of them show them looking ferocious, but if you start looking through Flickr for un-posed shots, they're mostly peaceful-looking, fairly cute little guys.iayorkhttp://www.iayork.com/MysteryRays/noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-69387061467177746062009-08-13T17:51:24.220-04:002009-08-13T17:51:24.220-04:00Whoa shit. I was digging the Taz-tumor model until...Whoa shit. I was digging the Taz-tumor model until that thing opened its mouth!!! Those things are biting machines.<br /><br />Maybe someone could breed the mean out of them...or select for a transmissible mouse tumour. I guess some of our implanted tumour models are kind of like that as they have been derived from serially mouse-passaged tumors...Although I don't know if any were passaged amongst MHC heterogeneous populations, like these wild Taz-tumors...Baymanhttps://www.blogger.com/profile/03436172198266062229noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-44277901294935070092009-08-13T16:31:16.475-04:002009-08-13T16:31:16.475-04:00I guess I'm suggesting something you already k...I guess I'm suggesting something you already know. Because these tumour cells have evolved to evade immunological rejection they may also lack the ability to recruit the immune system to fight off a virus infection.<br />The Tasmanian devil cancer might be a great animal model. Too bad those things <a href="http://www.youtube.com/watch?v=6_qh2DHg3Y8&feature=related" rel="nofollow">look like they would rip my face off.</a>Robhttps://www.blogger.com/profile/11878582460269426199noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-29923302207502773602009-08-13T14:56:10.195-04:002009-08-13T14:56:10.195-04:00Gardasil is a good example, probably the reason it...Gardasil is a good example, probably the reason it has worked where all other vaccines have failed is that it's actually a vaccine against a pathogen, not tumor cells.<br /><br />@Rob. Are you suggesting that infecting Tasmanian devil tumors with a virus would induce immunological rejection, despite the fact that MHC rejection has already failed?Baymanhttps://www.blogger.com/profile/03436172198266062229noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-70640625934788018192009-08-13T13:57:26.399-04:002009-08-13T13:57:26.399-04:00Yeah it always struck we as an odd approach, I mea...Yeah it always struck we as an odd approach, I mean if there is a good antigen, and the immune system has failed to react to it, what makes you think a vaccine would work? But I wonder if perhaps it would work in prevention, before the cancer evolves the ability to evade the immune system. Like Gardasil but with a self-antigen.Anonymous Cowardhttps://www.blogger.com/profile/13315733940344340689noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-55707424608766643632009-08-13T13:10:29.871-04:002009-08-13T13:10:29.871-04:00Smart immunologists work on oncolytic viruses.Smart immunologists work on oncolytic viruses.Robhttps://www.blogger.com/profile/11878582460269426199noreply@blogger.com