Healing Heat: Harnessing Infection to Fight Cancer

Modern immunology plus historic experiments suggest a better way to gear up the human immune system to battle malignant disease

Uwe Hobohm

Fever As Weapon

Sidebar: What the Literature Says

But fever is not recognized as a therapeutic tool in clinical settings. In fact, fever is a nuisance to patients and staff. Fever accompanies dangerous infections, so its removal is equated with removing danger. A proliferative infection can cause circulatory problems, and patients experiencing them need to be monitored closely. Multiple incentives persist to use an aspirin or another antipyretic to shut fever down.

But fever induced by sterilized pathogens or pathogenic substances is much less dangerous than a proliferative infection. Circulatory problems caused by Vaccineurin, a fever-inducing drug containing Streptococcus extracts used in German private clinics until the early 1990s, were extremely rare. These fevers usually lasted less than a day and then declined automatically.

Some clinical tests using PAMP have been pursued in recent years. That comes from the recognition that PAMP represents a novel group of substances that could be patented for profit. However, experiments involving PAMP have been guided by magic-bullet thinking favored by pharmaceutical companies. Important lessons from Coley and his contemporaries, including those related to fever, are not being adequately incorporated in the testing. Fever usually is suppressed as an adverse reaction during the tests. But that is not all.

PAMP therapies usually are tested in patients who have had prior chemotherapy, radiation therapy or both. These patients have compromised immune systems. Optimal results can only be expected in patients with noncompromised immune systems. Also, in contrast to a natural infection, where a mixture of PAMP molecules invades a host, only single substances are tested in the clinical trials. That’s the case even though vaccine research has taught us that living attenuated or sterilized pathogens induce a much stronger immune response than single antigens. Single PAMP, in general, will induce a much weaker immune response than would bacterial extracts.

When cancer worsens, PAMP treatment is stopped. But we know from Coley-era experiments that benefits sometimes take a long time to materialize. Instead, a fixed and not too small number of treatments should be pursued without interruption. The goal of such trials is to cure, which is admirable. But we know from other immunotherapeutic trials that sometimes a stabilization of the disease occurs, where malignant foci do not disappear but stop growing. Stabilization of disease should become an additional goal.

PAMP treatments are applied intravenously. But we have hints that stimulators of the innate immune system can be much more powerful when they are applied where the antigen is—namely close to the tumor. And in the present studies, PAMP doses are applied only a few times. It is likely that the innate immune system, lacking memory, must be stimulated again and again.

A different approach is in order. Multiple types of PAMP should be combined into a cocktail. PAMP should be injected close to tumors. If surgery is required, it might be advisable to start PAMP therapy before surgery, when antigen load is high, and continue it afterward to eradicate residual neoplasm. Fever should be allowed, if not stimulated.

On the Internet today, Coley’s toxins are celebrated as an unjustly ignored therapy ready and able to cure cancers. Such simplicity is a vast overstatement, since Coley himself had very mixed results. But we have much to learn from his experiments, from the suggestive epidemiology and from the records of spontaneous regressions. It is time to integrate what they teach with our improved understanding of the innate immune system. Otherwise, the full potential of PAMP therapy will not be leveraged.

There may be prophylactic potential here as well. Epidemiological studies suggest that a personal history that includes several infections with fever sometimes significantly reduces the likelihood a person will develop cancer later (see What the Literature Says). One potential explanation is that feverish infections reduce would-be malignant cells. If that’s true, the implications are profound.

Antibiotics must be applied immediately for life-threatening diseases such as lung infection or tuberculosis. But we must ask: Should we apply antibiotics and antipyretics (fever lowering drugs) early and for all minor infections? If we do not, more people will endure unpleasant days in bed. But quick alleviation of discomfort should be weighed carefully against the potential loss of long-term benefit.

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