First Safety

Meanwhile, human studies are tending to confirm findings in animals that the treatment does not induce its own problems. Immunization with normal ‘self’ proteins raises the concern that the body could lose its tolerance to self-proteins and start attacking itself. Alternatively, adding a vast excess of tumor proteins could potentially trick the body into thinking that tumor proteins are self, thus turning off any anti-tumor immune reaction that occurs naturally. But, says Srivastava, "we do not break tolerance or induce tolerance. We’re immunizing with the whole gemish of molecules but we only get a specific response. The prospect of doing harm is not there based on the human data thus far."

Srivastava notes that the immune system is constantly exposed to self-peptides without generating autoimmunity. Of course, it also fails to generate significant immunity to the tumor proteins without the help of the immunization procedure. This failure may be a result of immunosuppressing factors produced by many tumors, and the inaccessibility of hsps trapped inside the tumor cells. Once the hsps are administered as a treatment, they are highly efficient at helping turn on the immune system. "The receptor [for hsps] makes it possible," says Srivastava. "That is the magical element."

Antigenics is now conducting a phase III trial to treat kidney cancer, and phase I and II trials to treat many other types of cancer. Early trial results have been promising. For now the choice of cancer type reflects issues such as the relative inadequacy of current treatments and the logistics of patient recruitment. But Srivastava’s long-term plans are more ambitious. "Once we’ve proven that it works, we’ll essentially expand to every tumor type," he says. "Experimental work suggests there is no limitation."

continue...

Vaccinating against cancer