NEW YORK--If the immune system represents the front runner in
the fight against cancer, opinion remains divided on the best
way to harness it. Some researchers are betting on the interleu-kins;
others believe that the tumor cell itself must be altered to make
the immune system recognize it as the enemy.
In a briefing cosponsored by the Cancer Research Institute and
Immunex Corporation, Polly Matzinger, PhD, head of the Section
on T Cell Tolerance and Memory, National Institutes of Health,
expounded a novel theory on the mechanisms of immune response.
Discarding the notion that T cells attack what they recognize
as "nonself," she asserted that these lymphocytes are
instead programmed to recognize and respond to "danger,"
which she defines as anything that causes cell stress or lytic
It is this distinction, she claims, that explains why there is
no natural immune response to a tumor: A cancer cell is a normal
cell that has lost its growth control; it is neither undergoing
nor causing lytic cell death. Not only will it not activate an
immune response, it will slowly self-tolerize, ensuring its acceptance
by its host.
According to this proposition, current cancer vaccines fail to
elicit a sufficiently long-lived immune system response because
the tumor itself suppresses any response that is effected. The
vaccine may shrink the tumor for a while, but as the immune response
wanes, tumor growth resumes.
The answer, Dr. Matzinger believes, lies in employing an adjuvant
that will cause lytic cell death and thereby activate T cells.
This would be effective, she asserted, if the tumor is removed
and immunization delayed until new T cells, which have no immunologic
memory of the tumor cells, are produced.