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 cell death.
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.