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Vaccinating against cancer

By William Wells

If every cancer is different, why not try a personalized vaccine?

Exploiting differences

Most current cancer treatments are like blunt sledgehammers. They have some selectivity for cells that divide rapidly (like cancer cells, intestinal cells, and hair follicle cells), but largely fail to exploit the molecular differences that biologists have more recently defined as tumor-specific.

How can we target these differences? A company called Antigenics Inc.(New York, New York) is suggesting that the immune system is the answer. Differences are what the immune system is all about. Immune cells detect invading microbes based on the different proteins displayed on the microbes’ surface, and those difference trigger mechanisms that destroy the invaders.

Cancer cells are also different from normal human cells. For starters, cancer cell growth is uncontrolled — often cancer cells do not require special growth signals to multiply, and they do not stop growing when they contact other cells. For decades scientists have hoped that they could understand the molecular changes behind these differences, and exploit them to come up with more specific anti-cancer therapies.

Cancer cells often move around.

The idea of using the immune system as a more exact weapon has been around since 1893, when William Coley observed cancer regression after erysipelas infection. The infection, Coley presumed, had triggered the immune system to attack a protein that was similar on both microbe and cancer cell.

Coley’s experience was fortuitous, but, as molecular knowledge about cancer cells grew, scientists tried immunizing against cancer using specific proteins. Early success in animal models was followed by a failure to cross-protect — animals had to be immunized with material prepared from their own tumors — and suspicions that animal models were a poor simulation of human cancers.

Slowly the field of cancer immunotherapy has revived itself. The search for tumor-specific proteins has been long and hard, and many of the therapies being tested now are tissue- rather than tumor-specific. But renewed hope is coming from the use of human genome information to define tumor differences. "I think the time is right for these therapies to be taken to the clinic," says Michael Longenecker, senior vice president for research and development at Biomira Inc. (Edmonton, Alberta, Canada).

The number of companies searching for tumor-specific proteins is ever increasing. But Pramod Srivastava, an immunologist at the University of Connecticut and the scientific founder of Antigenics, is spurning the definition of tumor-specific proteins. "There is no reason to believe that those [tumor-specific] molecules exist," he says. Srivastava is sticking with the original observation that protection is often restricted to the animal from which the protein material was derived. His proposal is a personalized therapy based on, of all things, proteins that help cells respond to heat stress.


Vaccinating against cancer

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