One of the many lessons the world has been reminded of in the past few years is just how powerful vaccines can be. After all, prevention is better than cure, as the 16th century philosopher Erasmus famously said – although, as we’re finding out, vaccines can be pretty good at both.
That’s especially true with cancer vaccines – a relatively new area of medicine that some experts are calling “the cancer miracle.” And according to a new study in animals, published today in the journal Nature, one new cancer vaccine could be about to change the game once again, providing “protective immunity even against tumors with common escape mutations.”
In popular culture, “a cure for cancer” is often held up as the gold standard of scientific progress. But actually delivering on this soundbite is way more difficult than it sounds, since what we call “cancer” is actually a broad term covering more than 200 different diseases, each with distinct sub-types and variations as unique as the people they affect.
“Cancer is a complex disease, for which we won’t have a single cure,” explained Dr Matt Lam, Science Communications Manager at Worldwide Cancer Research, who wasn’t involved in the study. Each type and subtype of cancer requires “a unique approach to prevention, diagnosis, and treatment,” he pointed out, and even then, the disease is “highly adaptable … Cancer can spread to other organs, and it can become resistant to treatments that initially work.”
That’s why, for years now – much longer than you might think, in fact – some researchers have searched for a way to teach the body’s own immune system to fight cancer, a technique known as immunotherapy. The world’s first cancer vaccine came out in 2006, protecting against HPV-related diseases such as cervical cancer and various cancers of the head and neck, and recent years have seen an explosion of new and hyper-personalized vaccines for cancers all over the body.
But even these approaches have their drawbacks. “Most cancer vaccines target peptide antigens [specific protein cells expressed on the surface of tumors],” the authors of the new paper write, which is why these cancer vaccines have all been tailored to each disease and person – the precise nature of each antigen, and their ability to stimulate an immune response in the patient, is simply too diverse to make a universal cancer vaccine sound realistic.
But the new vaccine gets around this problem, the authors write, by “induc[ing] a coordinated attack by diverse T cell and natural killer (NK) cell populations.” These are two of our bodies’ first-line defenses against disease: NK cells in particular are named for their ability to hunt down tumor cells without any priming by antigens. The vaccine fires these cells into battle against two types of tumor surface protein, known as MICA and MICB proteins, which are expressed by a variety of human cancers.
Now, so far, the vaccine is really just mimicking what our bodies would do naturally when presented with a tumor – but then it does something extra-special. Usually, when T and NK cells get sent out to deal with cancer, they attack it by binding themselves to the MICA and MICB proteins on the surface of the tumor – and usually, the tumor will usually respond by jettisoning the affected proteins using a process called “slicing” or “cleavage”. But the new vaccine prevents that: “Vaccine-induced antibodies increase the density of MICA/B proteins on the surface of tumor cells by inhibiting proteolytic shedding,” explains the paper, stimulating the T and NK cells to go in and mount an orchestrated attack.
While the vaccine is yet to be tested in humans, the researchers say they have demonstrated its efficacy and safety in both mice and nonhuman primates.
“Notably, this vaccine maintains efficacy against … tumors resistant to cytotoxic T cells through the coordinated action of NK cells and CD4+ T cells,” write the team. “The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumors inhibits the later outgrowth of metastases.”
With such promising pre-clinical results, the next step is to trial the vaccine in human patients with cancer – and “a first-in-human clinical trial is being planned,” the paper notes. The vaccine may also work well in combination with radiation therapy, it adds, as “DNA damage enhances MICA/B expression by cancer cells.”
“We’ve gone through several cancer paradigms, so this comes down to a new approach,” nephrologist Dr Jason Fung told Global News back in 2018. “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.”