Generally speaking, rodents rarely receive any good press. From plague decimated medieval Europe to the modern housewife`s revulsion finding droppings in the pantry, rodents are not welcomed cohabitants. All this is true but on the plus side, they are definitely the unheralded foot soldiers in our war on various cancers and the substantial progress we have achieved in our understanding of almost every disease from obesity to diabetes even arthritis and substance abuse and aging. In 1981, a collaborative effort between universities in the states of Washington and Pennsylvania and at Oxford resulted in the first-time injection of purified DNA in to a single cell of a mouse embryo and the field of TRANSGENESIS was born.

There are several reasons mouse research is so valuable. Firstly, their tissues and organs are remarkably similar to our own especially in the structure of blood cells. They are definitely politically correct research models generating no mass public outcry as would occur with pet friendly species, dogs, cats, even monkeys. Its indisputable how rapidly they naturally reproduce and they are relatively small therefore cheaper to house and feed. The most frequently utilized subgroup is the “knockout mouse“ in which the activity of a gene or genes is removed allowing for numerically feasible study cohorts. With cancer research, two subgroups of gene modelling are used. Some are bred with a lack of tumor suppressing immune systems while others called ONCOMICE carry cloned oncogenes literally sealing their fate guaranteeing they will develop cancer.

The gatekeeper to the human immune system is the T cell a lymphocyte member of the white blood cell group. Once in contact with an alien protein, they network an immune response to repel the invader. Unfortunately, Cancer cells are clever at disguising themselves and acquire an ability to hide from the immune system but with the aid of our mouse allies, we`re getting clever too. One of the most dreaded cancers are the leukemias or “blood cell cancers“ occurring at any age, rapidly progressive and too often lethal. Recently announced new treatment protocol involves removing T cells from the patient then tagging them with “receptor“ molecules that target cancer cells. The revved up T cells are then placed back in the patient to seek out and selectively destroy the cancer cells. To date, too much of our cancer treatment has non-selectively destroyed a preponderance of normal cells. These targeting molecules are known as CHIMERIC antigen receptors and they are derived from specifically bred genetically engineered mice.

In recently released data from Seattle`s Hutchinson Cancer Research Facility, a relatively small number of cancer patients underwent this form of treatment. Criteria for inclusion was end stage leukemia with projected life expectancy reduced to 3 months. All patients were volunteers with full disclosure of the experimental nature of the protocol. Of the 35 patients with A.L.L acute lymphoblastic leukemia 95 % achieved complete remission. Remission by definition does NOT mean

cured and the disease with time may recur. The downside is 7 of the 35 experienced severe immune reactions requiring intensive care. Two did decease. In a further cohort of 40 patients with lymphoma, there was an 80% response with 50% achieving remission. In a third limited study of 3 patients with chronic lymphocytic leukemia, similar percentiles were achieved. Obviously it is impossible to extrapolate these remarkable results to a more generalized and substantive population at this early point and it is impossible to predict how long the remissions will remain but two indisputable conclusions are clearly available from this work. For the terminally ill there is now new hope and its happening at an exceedingly accelerated rate not previously possible before the ONCOMOUSE.

Written by: Dr. David Carll

Providing a fresh perspective for Hamilton and Burlington

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