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Biotech / Medical : HuMAB companies
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To: Icebrg who wrote (469)12/20/2002 5:37:24 PM
From: nigel bates   of 1022
 
Tumor penetration problems for mAbs.

Rick warned us about this ages ago. :-(

Rather more recently, I posted this link on the cancer thread.

medscape.com

Lots of interesting stuff; eg...

...In this approach, the pretargeting antibody is used to preferentially localize an enzyme molecule rather than a drug or radioactive isotope at the tumor site. The enzyme is designed to rapidly convert a large number of a low-molecular-weight prodrug (inactive drug) to its active (cytotoxic) form. Once the MAb/enzyme conjugate is cleared from the host circulation but remains localized at the tumor site, a high dose of prodrug can be administered where activation would preferentially occur at the tumor site rather than systemically. Since the drug is released extracellularly, it has the advantage over drug-targeting approaches in killing bystander cells as well as the MAb-targeted cell...
...Another interesting approach substitutes a humanized catalytic antibody for the enzyme component in the fusion protein.[101] The catalytic antibody can activate prodrugs derived from a variety of potent cytotoxic molecules such as doxorubicin, camptothecin, or a nitrogen mustard prodrug.[101,102] Since the activation site is unique to the catalytic MAb, no systemic activation can occur, allowing high input doses of extremely potent cytotoxic molecules that are activated at the tumor site...
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