immunomodulatoryoligonuceotides plus herceptin decrease breast cancer growth by 96%!!

[Lani]

Mol Cancer Ther. 2006;5:2106-2114
© 2006 American Association for Cancer Research
Research Articles: Therapeutics
Immunomodulatory oligonucleotides as novel therapy for breast cancer: pharmacokinetics, in vitro and in vivo anticancer activity, and potentiation of antibody therapy

Hui Wang1,2, Elizabeth R. Rayburn1, Wei Wang1, Ekambar R. Kandimalla4, Sudhir Agrawal4 and Ruiwen Zhang1,2,3

1 Department of Pharmacology and Toxicology, Division of Clinical Pharmacology; 2 Comprehensive Cancer Center; and 3 Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama; and 4 Idera Pharmaceuticals, Inc., Cambridge, Massachusetts

Requests for reprints: Ruiwen Zhang, Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, 113 Volker Hall, Birmingham, AL 35294. Phone: 205-934-8558; Fax: 205-975-9330. E-mail: Ruiwen.Zhang@ccc.uab.edu



Oligonucleotides containing CpG motifs and immunomodulatory oligonucleotides (IMO) containing a synthetic immunostimulatory dinucleotide and a novel DNA structure have been suggested to have potential for the treatment of various human diseases. In the present study, a newly designed IMO was evaluated in several models of human (MCF-7 and BT474 xenograft) and murine (4T1 syngeneic) breast cancer. Pharmacokinetics studies of the IMO administered by s.c., i.v., p.o., or i.p. routes were also accomplished. The IMO was widely distributed to various tissues by all four routes, with s.c. administration yielding the highest concentration in tumor tissue. The IMO inhibited the growth of tumors in all three models of breast cancer, with the lowest dose of the IMO inhibiting MCF-7 xenograft tumor growth by >40%. Combining the IMO with the anticancer antibody, Herceptin, led to potent antitumor effects, resulting in >96% inhibition of tumor growth. The IMO also exerted in vitro antitumor activity, as measured by cell growth, apoptosis, and proliferation assays in the presence of Lipofectin. This is the first report of the pharmacokinetics of this agent in normal and tumor-bearing mice. Based on the present results, we believe that the IMO is a good candidate for clinical development for breast cancer therapy used either alone or in combination with conventional cancer therapeutic agents. [Mol Cancer Ther 2006;5(8):2106–14]

[CherylS]

Woe, I think that is the longest word I have ever seen!

[Tom]

Gee Cheryl,

What's the matter with you? Didn't you see Mary Poppins as a child?

supercalifragilisticexpealladocious

I hope my spell-checker function is turned on...lol

[rinaina]

that's what i like about this forum...despite what we all are dealing with, we can all still laugh and have a sense of humor! G-d bless this forum!!!!!!

[CherylS]

You win by 4 letters. lol

[Tom]

Just so we don't forget the original article after I turned this thread into a yuk fest, Lani's post was a real mental booster to me.

How many agents, or groups of agents for that matter have produced a 96% reduction in tumor growth? None, that I have ever read about. This is a BIG deal. We are seeing more and more targetted therapies that don't slam you like the hammers of hell while they are helping you. Researchers are trying many different combinations of treatments with ones from the past and newly discovered ones, and getting promising results.

I just want to encourage everybody to do your best to hang on so we can all be there together when we hear that, "Today's the day", as a friend of mine, Mel Fisher in Florida said, when he finally discovered the Mother lode of sunken treasure that he had sought for so long. I believe that the answer to this horrible disease is close at hand. For sure it will be a bitter-sweet moment though, as we will remember with heavy hearts those of us here who did not make it to the Promised Land.

I am still trying to figure out the best ways to light a fire under the government to get more funding for cancer research in general. With all of the nonsense going on in the world today, those suffering from these diseases get put on the back burner. At least the natural enticement of capitalist greed on the part of the drug compaines keeps their feet to the fire. I am now recommending Glaxo stock to my friends who still play the market. They need only look at Genentech's chart over the years to see the light.

Sorry for getting so heavy on this subject, but I think about the cure every day of my life, for Mom, and for all of us that might one day deal with The Beast.

[rinaina]

Well said Tom. I for one will do my darndest to stick around for that promised day.

[heblaj01]

I,like everyone else, hope that this new experimental treatment posted by Lani will be successfully tried in humans.

But until the first signs of efficacy in patients, I now keep my optmistic hopes somewhat under lid when reading about early test results because of the time I became exceedingly enthousiastic back in 1998 only to be disapointed & then going through ups & downs of the development of the first antiangiogenesis drugs.
This was the time in 1998 when the world was stuned to hear that all tested human cancer cell lines responded dramatically to Endostatin or Angiostatin,the two naturally occuring endogenous molecules. And 60 to 80%of mice grafted with human cancers that were left to grow to 20% of their weight became so small as barely sensed to the touch. And the treatment could be stopped up to 50 times & each time the tumours would regress in a similar way. No apparent side effect.
Moreover when Endostatin & Angiostatin were combined the treated mice not only saw their tumour regress: they were cured. The success rate was 100%.
Since angiogenesis appears to be universally required by nearly all types of tumours to grow it made sense that Endostatin & Angiostatin would cure all of them.
No less than Nobel prize winner James Watson (of DNA fame) predicted that Dr Folkman (whose laboratory discovered Endostatin & Angiostatin) would cure cancer in 2 years.
Dr Folkman was more restrained. He said "if you are a mouse we can cure you".
Endostatin & Angiostatin each separately did show some anticancer activity & very low side effects in phase 1 & 2 trials by a private company holding the licenced rights on the drugs but they did not achieve the hoped for results.
In addition poor financial management, resulting in unresolved technical difficulties stopped the development of the drugs by this company & prevented the trial of the combined drugs. The real value of these 2 drugs is still unknown.
The mice experiments were not good enough models of human trials.
Often the breeds of mice are selected to reduce the number variables which
makes them remote models of human metabolism.
And the publication of early test results tends to insist more on their positive side than on their negative side since future financing of continuing research is dependant on good results.

This said I am nevertherless really hopefull that one or more of the many new angles currently tried to beat cancer will succeed.
And the currently available drugs which are more effective & less toxic than the older ones are usually providing the long term bridge to future treatments.