So many breathless announcements of treatments that work in vitro, or in animal studies, and are never heard from again. Wake me up after human trials.
[From Science] Cancer researcher Tyler Jacks of the Massachusetts Institute of Technology > in Cambridge says that although the new study is promising, more research > is needed to see whether the results hold true in humans. "The > microenvironment of a real tumor is quite a bit more complicated than the > microenvironment of a transplanted tumor," he notes, "and it's possible > that a real tumor has additional immune suppressing effects." Original paper "The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors<http://www.pnas.org/content/109/17/6662.full> " And as usual in science, not everyone is so impressed On the mechanism of CD47 targeting in cancer <http://www.pnas.org/content/109/42/E2843.full> Finally, our own recent studies (5<http://www.pnas.org/content/109/42/E2843.full#ref-5>) > applying the well-established syngeneic B16 melanoma cell model to > SIRPα-signaling death mutant mice did not demonstrate any effect of the > CD47–SIRPα signaling axis on tumor metastasis and outgrowth. However, when > therapeutic antibodies against the melanoma cells were injected, the > SIRPα-mutant mice cleared the tumor cells much more effectively than > wild-type animals. Furthermore, in vitro ADCC experiments of human > neutrophils toward Trastuzumab-opsonized breast cancer cells showed an > enhancing effect of CD47–SIRPα antagonists in the presence, but not the > absence, of cancer therapeutic antibodies. This result suggests that > targeting CD47–SIRPα interactions may be beneficial in combination with > antibody therapy in cancer. However, the evidence that targeting the > CD47–SIRPα axis may also work in the absence of therapeutic antibody seems > incomplete and contradictory. and a reply Reply to Soto-Pantoja et al. and Zhao et al.: Targeting CD47 on human solid tumors <http://www.pnas.org/content/109/42/E2844.full> We strongly disagree with Zhao et al. (7<http://www.pnas.org/content/109/42/E2844.full#ref-7>) > that targeting the CD47–SIRPα interaction with anti-CD47 mAbs does not > produce a therapeutic effect in the absence of a second, cancer-specific > antibody. We have demonstrated that anti-CD47 mAbs alone enabled the > phagocytosis ≥24 patient tumor samples in vitro and inhibited tumor growth > or metastasis of ≥10 solid tumors in vivo. We believe this result is beyond > sufficient to demonstrate that a second antibody is not required to produce > a therapeutic response. A second, cancer-specific antibody may further > enhance the efficacy of anti-CD47 mAbs, but it is not required > (8<http://www.pnas.org/content/109/42/E2844.full#ref-8>). > It is possible that blockade of CD47–SIRPα interactions, in the absence of > an intact Fc region, may not be as effective at producing a significant > antitumor response. However, the members of the van den Berg laboratory > themselves have shown that F(ab′)2 fragments prepared from anti-CD47 mAbs > can induce the phagocytosis of human cells > (10<http://www.pnas.org/content/109/42/E2844.full#ref-10>). > In no way do these issues detract from the conclusion of our papers > (1<http://www.pnas.org/content/109/42/E2844.full#ref-1>), > that anti-CD47 mAbs can inhibit the growth and metastasis of solid tumors, > especially of human origin. Most interesting to me is to contrast the breathless tone of the Fox/NY Post/Murdoch "reporting" with the facts themselves as contained in the paper. -- Charles On Sat, Mar 29, 2014 at 3:49 AM, Udhay Shankar N <[email protected]> wrote: > Researchers might have found the Holy Grail in the war against cancer, a > miracle drug that has killed every kind of cancer tumor it has come in > contact with, the New York Post reported. The drug works by blocking a > protein called CD47 that is essentially a "do not eat" signal to the body's > immune... > > > http://www.foxnews.com/health/2013/03/27/scientists-find-treatment-to-kill-every-kind-cancer-tumor/?intcmp=trending > > -- > ((Udhay Shankar N)) ((via phone)) >
