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
tumorshttp://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
(5http://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.
(7http://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
(8http://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
(10http://www.pnas.org/content/109/42/E2844.full#ref-10).
In no way do these issues detract from the conclusion of our papers
(1http://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 ud...@pobox.com 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))
