As for treating other cancers, some, including most pancreatic and colon cancers, remain difficult to treat with a personalized vaccine because of their biochemical profile. Drugs used in targeted gene therapy operate by inhibiting one or more cellular processes. But pancreatic and colon cancers are almost always associated with a KRAS gene mutation. The KRAS oncogene activates the PI3K enzyme pathway (involved in cell growth, proliferation and survival) and the MEK/MAPK pathway (a process that governs the way growth factors bind to the cell surface). In the KRAS mutation the oncogene is effectively always turned on, making it impossible to alter cellular processes it activates.
"In general, cancers like pancreatic cancer that almost always have a KRAS gene mutation have been quite refractory. That would of course change overnight if there were a promising way to molecularly target KRAS abnormalities," says Daniel Haber, director of the MGH-East Cancer Center.
For patients who respond well to these vaccines, however, cancer could become manageable, even if it's not curable, Haber says.
To be considered as a candidate for immune treatment, cancer patients must first undergo a successful course of targeted chemotherapy. This means that only patients who have responded to conventional treatment are eligible. Patients in clinical remission—whose tumors have disappeared or are significantly reduced in size—are given a course of immune treatment after a six-month rest period following chemotherapy. In the most successful of the Phase III lymphoma clinical trials, the course of treatment consisted of seven immunizations given over 24 weeks.
Although a standardized treatment protocol has not yet been developed—and it will probably vary according to the type of cancer involved—managing patients who respond to the vaccine promises more hope than does treatment with gene-targeted chemotherapy alone. It's the next bridge on the path to a cure. Theoretically, patients who have responded to one course of autologous vaccination could respond very well to a booster vaccination, if need be, somewhere down the road, or as planned maintenance therapy to prevent relapse.
Adapting ahead of cancer
Another big challenge looming ahead for personalized cancer immunotherapy is the disease's adaptability. "Cancers evolve in response to therapy," Haber says. "Even promising targeted therapies are limited by the development of drug resistance."
Even novel attacks on cancer can end up as an arms race. Controlling cancer rests on clinicians' ability to monitor changes in their patients. If one treatment becomes disease-resistant, catching it quickly and changing strategy can make all the difference to patient's prognosis.
Nevertheless, trying to develop new therapies based on what treatments will look like in the coming decade is a nearly impossible task, points out Michael Stratton, joint head of the Cancer Genome Project and professor of cancer genetics at the University of London's Institute of Cancer Research, who has been working on developing finely targeted cancer treatments since identifying the BRAF oncogene in 2002.
"Here it is the 10th anniversary of the human genome, and I have PhD students in my lab who say 'I can't understand how an old man like you possibly worked on this stuff before the genome was decoded. Why did you even bother?'" he says. But Stratton is convinced that in a few years time, once the full pattern of the cancer genome is revealed, his next group of students will ask the same question about the present state of research. "These are transformative times," he says. "Some pathways to the answers are clear. Most aren't."
*Correction (6/30/10): This sentence was edited after posting. It originally erroneously stated that the National Cancer Institute sponsored BiovaxID's development and that Genitope Corp., and Favrille, Inc., were involved in the phase III clinical trials.