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Summary

VirRx is creating novel drugs to treat many different forms of human cancer. We have taken a common cold virus, named adenovirus, and changed some of its genes such that it will attack and destroy cancer tumors without harming normal tissues in the body. This modified virus is termed a "cancer gene therapy vector". VirRx's "cancer gene therapy vectors" function on a completely different principle from the traditional methods of cancer treatment, namely surgery, chemotherapy, and radiation therapy. The VirRx vectors may be especially useful for those patients who have failed other treatments.

What is cancer?

Humans begin as a single cell, a fertilized egg, which has two copies of the full complement of about 40,000 genes. Genes form the blueprint for humans, and are embodied in long linear molecules termed "DNA". The information in a gene is translated into another linear molecule termed a "protein". Each gene specifies a different protein. Proteins are the workers of the cell; for example, some proteins carry out chemical reactions that allow the cell to extract energy out of food, other proteins provide the cell with structure.

The original cell (the fertilized egg) divides into two cells, which in turn divide into four cells, which then divide into eight cells, and so on. This process of cell division is termed "proliferation". As the cells in the embryo proliferate, some of them begin to express different subsets of genes such that different groups of cells eventually become different tissues of the body.

After the tissues form, for example the lung, the vast majority of cells in the tissue stop dividing. These cells express the subset of genes coding for proteins that allow the cell to carry out the various functions of the lung. Cell division is held in check by several hundred key regulatory proteins that block different steps in the cell division process.

In cancer cells, some of the proteins that block cell division lose their ability to function. This loss of function occurs when chemical changes occur in the DNA molecule containing the gene that specifies the protein. These changes are usually caused by highly reactive chemicals that enter the body and "mutate" (alter) the DNA. Such chemicals are found in cigarette smoke, certain foods, and can even be produced by the multitude of chemical reactions that naturally occur in the body.

In simple terms, cancer cells that have mutations in these key regulatory genes begin to proliferate into cancerous tumors. These cancer cells become less like mature tissue cells and more like embryonic cells. As they continue to divide, some cancer cells acquire the ability to break away from the original tumor and form new tumors in other parts of the body. This process is termed "metastasis". For example, primary colon cancers will often metastasize to the liver to form secondary cancers.

Treating Cancer with Surgery, Chemotherapy, or Radiation Therapy

If tumors can be detected early, especially when they are still primary cancers, they can often be treated successfully. The tumor may be removed by surgery, and/or it may be treated with specialized chemicals or radiation. With chemotherapy or radiation therapy, the rationale is to kill the cancer cells while causing as little damage as possible to normal non-cancerous cells. Patients will often become quite sick because these treatments do in fact cause some damage. Depending on the type and stage of the tumor, these treatments may be very efficacious. Tumors may vanish, never to appear again. However, in many cases, cancer cells will develop that have undergone genetic changes that make the cells resistant to the treatment. These cancers have a poor prognosis.

Treating Cancer with Cancer Gene Therapy

VirRx scientists are pursuing a totally different approach, termed cancer gene therapy, to treat cancer. In this approach, VirRx has taken advantage of millions of years of evolution of one of the viruses that causes the common cold. This particular virus is termed adenovirus because it was originally isolated from adenoids. Adenovirus is relatively simple in structure, consisting of a single DNA chromosome of 34 genes surrounded by a protein shell. Adenovirus causes mild or even asymptomatic upper respiratory tract infections in young children, resulting in life-long immunity. When it infects cells, the virus enters the cell and forces it to produce many more virus particles. This process is termed virus "replication". The virus then disrupts the cell, infects other cells, and repeats the process.

Using genetic engineering methods, VirRx scientists have modified some of the adenovirus genes such that the virus will attack only cancer cells in the body. The modified virus is termed a "vector". VirRx has constructed and characterized more than 10 different vectors, each with different properties. One genetic change takes advantage of two basic properties of cancer cells, namely that the cells are proliferating and resemble embryonic cells. Thus, a subset of the adenovirus genes is altered such that the vector can only replicate in cancer cells. The vector will not replicate in normal cells, which are not proliferating and are fully mature. Some of the VirRx vectors will only replicate in cells of certain types of cancer. With all the vectors, another adenovirus gene has been changed such that the vector can disrupt the cell very efficiently after new vector particles have formed. This feature increases the ease with which the vector can spread from one cell to another.

As a first step to treating cancer the vector will be injected directly into the cancerous tumor. The vector is expected to infect the cells in the tumor, replicate in these cells, disrupt the cells at the culmination of replication, and spread to other cells. In a few days or weeks, the vector should spread to all the cells in the tumor, eliminating the tumor. The vector cannot replicate in the surrounding normal cells, so these cells will not be affected. Thus, the vector is targeted specifically to tumors.

VirRx's vector system should be effective against many different types of human cancer. In initial applications, it should be especially valuable for those cancers that have become resistant to chemo- or radiation therapy, and/or that cannot be removed with surgery. The vector could be used alone or in combination with traditional therapies.

VirRx has validated its vector system in a large series of experiments with human cancer and normal cells growing in the laboratory. VirRx has also shown that the vectors are effective against cancers growing in experimental mice. VirRx plans to test one or more of its vectors in a Phase I trial for human cancer. This trial will address the safety and efficacy of the vector.