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Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Computational techniques can be used to evaluate a new class of targeted cancer-killing drugs.  Researchers are now using high-powered computers to determine
how substances known as recombinant immunotoxins can best be modified
in order to attack and kill malignant tumours while doing minimal harm
to a patient's healthy cells.

Scientists at the Florida A&M University-Florida State University decided that because cancer is a disease of tremendous complexity, the analysis and
interpretation of data demanded sophisticated, specialised computational
methods and looked at new ways of creating effective models.

Recombinant immunotoxins are new drugs that are being
tested in clinical trials for certain types of cancer therapy.  They
consist of tiny fragments of antibody proteins that are fused at the
genetic level to toxins produced by certain types of bacteria, fungi or
plants.

V4n4_fig1
Image from: Advances in Targeted Cancer Therapies

Schematic diagram of the basic unit of immunog...Image via Wikipedia

Once injected into the body, the antibody portion of the immunotoxin
targets specific proteins, called antigens, that are massively
expressed on the surface of cancer cells.  These cells are
subsequently killed by the accompanying toxins. Normal, healthy cells,
meanwhile, are not recognized and are spared.  However, numerous factors can decrease the immunotoxins' effectiveness, including:

  • The large size of some immunotoxin molecules can hinder their ability
    to move to the targeted location to bind readily with cancer cell
    proteins, leading to efforts to reduce their size.
  • The immunotoxin molecules' stability in the bloodstream and in the
    extracellular matrix can affect their length of time in circulation and
    in tumor tissues, respectively, thereby determining their effectiveness
    at killing the optimal number of cancer cells.
  • The rate at which immunotoxins bind with malignant cells and the
    relative amount of antigens expressed on the cell surface are
    especially critical factors, because an imbalance in those two factors
    may result in over-bombardment of a single cancer cell with excessive
    numbers of immunotoxins, leaving many other cancer cells unharmed. The
    opposite scenario also is possible: If not enough immunotoxins bind
    with malignant cells, too few cells will be killed with each dose.

The level of anticancer drug doses that can be given to any
patient is limited by immunogenicity, ie the immune response that
results.  It is essential to explore how the efficacy of recombinant
immunotoxins can be enhanced without resorting to escalating doses. 

The computational research has enabled quantification and
development of models describing many of the factors that influence
immunotoxins' behaviour in the body.  This knowledge is essential in order to develop immunotoxin drugs that might one day be
approved as a standard treatment for cancer patients.

Sources:

Annals of Biomedical Engineering
FSU

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2 Responses to “Can computers be used to improve cancer-fighting drugs?”

  1. Stales

    This is incredible stuff! As a three time cancer survivor, I’m glad to see advances in cancer therapies. Thanks.

  2. Sally

    Thank you for your comment!
    So glad to have you with us still 🙂

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