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ImmunoGen, Inc. Message Board

  • sy3dney sy3dney Jul 24, 2006 12:32 PM Flag

    New CNTO app?

    What the h is an LTL? New CNTO app?

    In a July-Aug '06 publication, (an 11 page article entitled A Review of Antibody Therapeutics written by CNTO scientists back in Oct., '05), they review 6-7 different methods being explored by the industry to fight cancer. The last 4 pages covered Immunoconjugates as Cancer Therapeutics with the last one and a half pages covering Enhancing Drug Delivery Through Ligand-Targeted Liposomes.

    Excerpts follow --

    Many cancer therapeutics are potent cytotoxics, but systemic delivery of these drugs results in cytotoxic activity against both the tumor cells and healthy cells throughout the body. Exposure of healthy cells to cytotoxics causes undesirable side effects the limit drug dose and/or dosing frequency, and this ultimately constrains drug efficacy and tumor control. Strategies that increase the therapeutic index of such drugs and reduce their toxicity to the patient are highly desirable. Ligand targeted liposomes (LTL) are one way in which the biodistribution and uptake of a cancer drug can be altered favorably to achieve these goals. LTLs also represent another strategy by which the targeting power of antibodies can help create more effective anti-cancer therapeutics.

    Tumors differ in many ways from normal tissues, but one key difference that can be exploited by liposome technologies is the tumor vasculature is defective and leaky. Normal blood cells are comprised of endothelial cells with tight junctions that do not permit liposomes to extravasate to neighboring tissue. However, the vessels in tumors are permeable, with pores that range from 100-800nm in diameter. This raised the possibility the small liposomes, on the order of 60-150nm, could traverse the tumor vasculature and deliver toxic payloads directly to the tumor. In addition, tumors lack lymphatic drainage, so liposomes are not readily cleared from the tumor and can continually accumulate.

    The article goes on to talk about the various +s and -s in the design of an effective molecule, and ends with --

    For example, LTLs designed with antibody fragments specific for CD-19, Her2
    => and B1 integrins,
    among others, all show significantly enhanced anti-tumor activity compared with non-targeted liposomes. The increased efficacy observed with LTLs in multiple model systems strongly suggests that this advance in liposomal technology may have clinical benefit, and it is expected that such novel drugs will soon move into clinical trials.


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