Pharma Strategy Blog

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.

Image from: Advances in Targeted Cancer Therapies

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