Late last month, researchers at Stanford University released the findings of their latest study that showed a vaccine injected into mice with metastatic cancer was effective in eliminating all traces of the disease in the rodents. They believe this strategy could work to both prevent the recurrence of cancer as well as head off tumour development as a result of genetic mutations like BRCA1 and 2.
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Meanwhile, an immuno-oncology company in Florida is currently clinically testing a vaccine specifically for triple-negative breast and ovarian cancer. It uses what they call a novel approach that stimulates both helper T cells and killer T cells (T cells are subtypes of white blood cells that play a central role in immunity) to target tumour cells.
And most recently, a UC San Francisco study found that a cancer-killing virus may be effective in targeting cancer cells as well as alerting the immune system to a tumour. An engineered virus based on the vaccinia cowpox virus (which is harmless) has been shown to attack cancer by damaging the blood vessels that feed tumour growth. Researchers believe this virus could be used as a vaccine.
What these findings point to is a collective promising development in the field of cancer immunotherapy, of which vaccines are a component, that could radically change how cancer is treated and prevented from recurring. But here’s the kicker — they’re nothing new.
But if Coley was immunizing people over a century ago, why haven’t vaccines been used (and perfected) since then?
“The struggle in the past has been that people were using cancer vaccines like chemotherapy. But when you think about vaccines and infectious disease, we don’t treat active infections with a vaccine, we use them to prevent the development of infections.”
Peter Hoang, CEO of TapImmune, the company working on the breast and ovarian cancer vaccine, echoes her statement.
Couple this misguided approach to using vaccines with the fact that the medical community was mired in looking for genetic clues to cancer for the past two decades, and you’ll see why it has taken this long to bring this game-changing treatment to fruition.
“We’ve gone through several cancer paradigms, so this comes down to a new approach,” says Dr. Jason Fung, a nephrologist and author of The Obesity Code. “Paradigm one was chemotherapy, radiation and surgery, which works but only to a certain extent. Paradigm two looked at the genetic defects of cancer, and it was an approach that went nowhere and set us back a lot of money and about 20 years. Now we’re in paradigm three with cancer vaccines and they’re very exciting.”
Fung says the approach of paradigm two, which looked at the cancer genome, went nowhere because researchers were looking to isolate two to three genes that they could fix. The problem was there were a lot more genes — like 200 — and even between two patients with the same breast cancer, there were hundreds of different genetic mutations. In fact, some have referred to cancer tumours as snowflakes because no two are alike.
But one doctor’s waste of time is another’s vital step in understanding the disease.
What are cancer vaccines?
A branch of cancer immunotherapy, which is a type of treatment that uses the body’s natural immune system to target and destroy antigens, cancer vaccines are used to either prevent or treat the disease. They can be autologous, which means they are made from cancer cells removed from the patient, or allogenic, which are made for a certain type of cancer. As can probably be deduced, autologous vaccines are much more expensive to produce.
To date, there are two vaccines widely used in Canada to prevent cancer: the HPV vaccine (Gardasil and Cervarix) and the hepatitis B vaccine. The former is a prevention against the human papillomavirus, which is linked to head, neck, throat, mouth, cervical, vaginal, vulvar, anal and penile cancer. The latter protects against hepatitis B-related liver cancer.
In addition, Provenge, a vaccine used to treat advanced prostate cancer that has stopped responding to hormone therapy was approved by the FDA in 2010, and one clinical trial in Canada is testing it for therapy in kidney cancer. While it doesn’t cure prostate cancer, it has been shown to extend a patient’s life by several months.
Both the HPV and the hepatitis B vaccine have proven to be immensely successful. Although the nature of HPV makes it difficult to track infection rates and health complications (ones that lead to cancer), some experts say that the introduction of the vaccine in conjunction with increased pap testing has unseated cervical cancer from the number-two female cancer in Canada.
Why are we focusing on them now?
Part of the excitement with cancer vaccines is due to the development of immune checkpoint inhibitors, a type of drug that takes the brakes off our immune system and allows it to attack cancer cells.
(Our immune system is responsible for differentiating between normal cells and foreign ones — and attacking the foreign ones. But in order to prevent it from going after every cell, it uses checkpoints. Unfortunately, cancer cells are adept at using these checkpoints to evade attack.)
“We now have tools that we can team up with vaccines, like immune checkpoint inhibitor antibodies that can allow us to create a small response and amplify it. Several studies and animal models have shown great promise in eradicating tumours when you use [the two modalities together],” Disis says.
Which is what TapImmune is banking on.
“What we’re finding is that immune checkpoint inhibitors work well in cancers with high rates of DNA mutation, like skin and lung cancer, but the problem in tumours like ovarian and breast cancer is that when you take the brakes off the immune system, there are low mutation rates and the T cells don’t see them,” Hoang explains. “We need native T cells to aid in the fight and that’s what our technologies do. We can drive the amount of antigens and better prepare the body’s T cells to respond more strongly in the fight against cancer.”
Hoang’s vaccine is targeted at women who are in remission because these cancers have such a high rate of recurrence. Approximately 70 per cent of women with ovarian cancer will have a recurrence, and those with triple-negative breast cancer are more likely to have a recurrent form of cancer outside the breast in the first three years.
“For those women in their first remission, we give them a vaccine that will help the immune system recognize cancer when it reoccurs, and increase the time that she’ll remain disease-free,” he says.
Although this sounds incredibly promising, some experts have their doubts.
“Don’t underestimate that cancer is very cunning and it finds ways of escaping vaccination,” says Dr. Tak Wah Mak, director of the Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital in Toronto. “One of the potential problems is that you have to get the T cells into the tumour, and that’s been challenging in cases of ovarian cancer in particular. If the T cells don’t get to the tumour, it’s a moot point if the patient is vaccinated.”
He calls these “notorious” cancers to treat and advises not to underestimate the evolutionary ability cancer cells have to survive what’s “thrown at them.” He also points out that TapImmune is not the first company to attempt this.
How long will it be before cancer vaccines are commonplace?
Cancer vaccines could become a main line of treatment sooner than you think — thanks in part to funding. TapImmune, for example, received a $13.3-million grant from the U.S. Department of Defense, and Hoang estimates that if all goes well, the ovarian cancer vaccine could be approved in three years’ time.
“Right now, we’re in a development stage and in mid-level clinical trials,” Disis says. “If you look at the landscape, there are many more vaccine companies than ever before, and most are in phase-two clinical trials and rapidly progressing to phase three. I expect we’ll see more approvals within the next five to eight years.”