camels(!), bacteria help out making new anti-her2 "nanobody" drugs

[Lani]

Tiny antibody fragments raised in camels find drug targets in human breast cancer cells
[Eureka News Service]

A new discovery published online in The FASEB Journal promises to help physicians identify patients most likely to benefit from breast cancer drug therapies. If the compound, called "Nanobody," proves effective in clinical trials, it would represent a significant advance for breast cancer drug therapy because some drugs are effective only in some people. In addition, some drugs have side effects that may cause damage to vital organs, making it more crucial for physicians to get the right treatment to the right patient the first time around.

"What makes Nanobodies so promising is that they are robust, small enough for rapid elimination from the body, and easy to produce at a relatively low cost," said Ilse Vaneycken, M.Sc., a researcher involved in the work.

To make this discovery, Vaneycken and her colleagues started with the target of the therapeutic drugs (HER2) and immunized a dromedary camel to raise special antibodies unique to this species. Next, all unnecessary parts of the camel's antibodies were removed and cloned in bacteria. Of 100 million bacterial clones, the team selected those that produced the 40 Nanobodies that recognized? or bound to?the same site targeted by therapeutic drugs. Of this group, the team screened for compounds that picked out breast cancer cells bearing the genetic tag HER2. Their lead compound did just that, and without blocking access to cancer-killing drugs now in use. Other properties of Nanobodies, such as good expression, stability, and visibility enabled breast cancer tumors to be stained and seen rapidly?were also exploited.

"The scientists went over the hump to get to the lump so to speak," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This technique not only promises to help doctors target cancer cells with effective drugs today, but to pick out other discrete cancer targets in the future."

ABSTRACT: Preclinical screening of anti-HER2 nanobodies for molecular imaging of breast cancer
[Federation of American Societies for Experimental Biology]

Accurate determination of tumor human epidermal growth factor receptor 2 (HER2)-status in breast cancer patients is possible via noninvasive imaging, provided adequate tracers are used. In this study, we describe the generation of a panel of 38 nanobodies, small HER2-binding fragments that are derived from heavy-chain-only antibodies raised in an immunized dromedary. In search of a lead compound, a subset of nanobodies was biochemically characterized in depth and preclinically tested for use as tracers for imaging of xenografted tumors. The selected compound, 2Rs15d, was found to be stable and to interact specifically with HER2 recombinant protein and HER2-expressing cells in ELISA, surface plasmon resonance, flow cytometry, and radioligand binding studies with low nanomolar affinities, and did not compete with anti-HER2 therapeutic antibodies trastuzumab and pertuzumab. Single-photon-emission computed tomography (SPECT) imaging quantification and biodistribution analyses showed that 99mTc-labeled 2Rs15d has a high tumor uptake in 2 HER2+ tumor models, fast blood clearance, low accumulation in nontarget organs except kidneys, and high concomitant tumor-to-blood and tumor-to-muscle ratios at 1 h after intravenous injection. These values were dramatically lower for an irrelevant control 99mTc-nanobody and for 99mTc-2Rs15d targeting a HER2- tumor.

[PinkGirl]

Anybody thinking what I'm thinking????

[chrisy]

WHAT - with tiptoe????

[PinkGirl]

Well ... Tiptoe and all the other Chinese hamsters gave us Herceptin ... now we're going to get some kind of anti-body from a camel ... just wondering if I need to buy another critter and a new journal ...

[SoCalGal]

"Went over the hump to get to the lump?" One fish, two fish, her2nue fish? Is this a study by Dr Suess?

[PinkGirl]

and they are small enough for rapid elimination from the body ... is that the camel's body???? Where do they come out???

Does that mean I might be able to get through the night without a visit to the bathroom for potty and a drink?


StephN - who is a little puffy in Bali due to the very high humidity ...

[pibikay]

Thanks Lani.I always find your postings informative

[PinkGirl]

That's the up-side StephN ... the down-side is getting that
big hump. Makes you wonder if camels have low estrogen and
the hump is actually from osteoperosis ... doubt they drink any
milk but they get a lot of D from the sun ...

[SoCalGal]

"...the down-side is getting that big hump"
I would respectfully disagree
-A big hump fan

[PinkGirl]

Yur bad FloriGirl..... are you also a fan of Wednesday ... hump day?

[tricia keegan]

Thanks Lani!

Pink, I want a glass of whatever you were drinking when posting the above lol!!..oh, and if you find the study on toasted marshmallows and Mothers with wide hips please pass it on!