The March 1993 Scientific American contained
an article on "Teaching the Immune System to Fight Cancer." The
author, Thierry Boon, director of the Ludwig Institute for Cancer Research
in Brussels, is working on a genetically-engineered vaccine to prompt white
blood cells to attack a person's cancer.
It may be years before such a vaccine is ever administered to patients.
But not all cancer vaccine research is so theoretical or high-tech. We recently
interviewed Duncan L. McCollester, MD, PhD, a Cambridge University-trained
researcher/internist who holds U.S. patents on a cancer vaccine called the
Autologous Anticancer Antigen Preparation (AAAP). He has been developing
it since the 1960s.
Q. How does your work on AAAP compare to the work that Dr. Boon reports
in Scientific American?
A. The object of our two approaches is identical. Boon's article is fine,
but its approach is circuitous, highly technical and, for now, of limited
applicability. Our approach, on the other hand, is very simple and direct.
It may also reveal the true cause of most cancers—the failure of the
immune system.
Q. Why doesn't the immune system recognize malignant cells as foreign
and just destroy them?
A. Most of the time, it does. What we call clinical cancers are the failures
of the immune system. You have to understand that there are two basic kinds
of immunity. The first is humoral, i.e., antibodies sent through the blood
by "B" lymphocytes (white blood cells). These are like guided
missiles that home in on and destroy foreign substances. Humoral immunity
is especially effective against small entities such as viruses. But it is
the second kind of immunity, based on "T" white blood cells, which
is needed to kill relatively big things, like cancer cells.
Q. Immunity depends on a sophisticated recognition system. How does
the immune system monitor cells to determine if they are "self"
or "non-self"?
A. Within all cells there is an ingenious mechanism that takes proteins
from inside and displays them as a kind of `flag,' announcing that cell's
allegiance to self. This flag is called the histocompatibility antigen.
When the immune system finds cells displaying a foreign flag (either because
they are infected or have become malignant) in addition to the flag of self,
it sends lethal T cells to kill them on contact.
Q. So how does cancer evade this sophisticated surveillance system?
A. Normally, it doesn't. But evolutionary pressures are at work. Some
malignantly transformed cells acquire the means to evade destruction. They
release a barrage of non-self material, waving foreign flags, into the blood.
This tricks the immune system into switching production from effective cellular
immunity to useless humoral antibodies. As we said, humoral antibodies cannot
kill cancer cells. So thanks to this ruse, and there are probably others,
malignant cells can multiply and form tumors.
Q. How can this knowledge be used to formulate a cancer vaccine?
A. An effective vaccine must contain both cancer-derived proteins and
display the `flag of self.' It must not contain any proteins that would
trick the immune system into producing those useless humoral antibodies.
Finally, it has to have a `kicker,' to strengthen the stimulus of the
cancer protein. We use manganese, essential for life. This attracts immune
system cells to the vaccine injection site.
Q. How does this approach compare with Boon's?
A. Boon has identified a gene that produces the same foreign flags in
many melanoma cells. This is a notable technical achievement. He has also
identified some melanoma patients who have T cells that might destroy their
melanomas. But the practicality of this high-tech vaccine has yet to be
determined.
Our approach concentrates on substances already in-place on the surface
of cancer cells. We separate normal cell surface structures from other parts
of the cell and then remove everything that can lead to the production of
worthless humoral antibodies. The final product, isolated cells surfaces,
are very stable.
AAAP must be individually crafted from a portion of each patient's tumor.
To make AAAP, we need four steps: we break up (disaggregate) a tissue sample,
disrupt the cells, recover the membranes and finally add manganese. Most
importantly, we are not just at the theoretical level. In a number of cases,
AAAP has already demonstrated long-term clinical efficacy against a variety
of cancers.
Q. What is the next step?
A. We're ready to start testing and have had good cooperation from the FDA.
But we urgently need financial support.
