A new way of tricking the body's own immune system to attack cancer cells.
Image: Damian Ryszawy/Shutterstock
Right now the odds are not much better than 50-50 that you, in particular, will have cancer at some point. And, aside from not smoking (especially) and generally trying to live healthy, there also isn't a whole lot you can do to tweak those odds in any dramatic way. Even among smokers, obsessive sunbathers, and vegetable haters, cancer winds up being pretty random. The dice can be loaded (sometimes a lot), but they are still dice.
There are so many cancers and so many things that can work in concert or independently to increase a person's cancer risk—to say nothing of the sheer scope and scale of cancer as an epidemic—that the idea of a universal cancer vaccine seems pretty far-fetched. Hell, given the vast and increasingly effective ecology of cancer treatments, a vaccine doesn't even seem fair (especially if you happen to be a pharmaceutical corporation pushing those often extremely expensive treatments).
Nonetheless, a universal cancer vaccine is something being actively pursued and it may prove to be attainable after all. In a paper published Wednesday in Nature, researchers from Johannes Gutenberg University describe the development of a potential vaccine based on the immune system's natural responses to viral infection. In early experiments based on mouse tumor models and three human patients with advanced melanomas, the vaccine, which essentially consists of nanoscale poison darts with of RNA payloads, was able to induce specific anti-tumor immune responses.
Immune responses that would normally go unprovoked by cancer cells are tricked into thinking there's a virus on the move
"Why is it so difficult to effectively vaccinate against cancer?" write Dutch immunologists Jolanda de Vries and Carl Figdor in an accompanying Nature commentary. "One reason is that cancer cells are similar in many ways to normal cells and the immune system avoids attacking the self. Only relatively modest immune responses occur with vaccines containing antigens that are also expressed on healthy tissue. Strong immune responses can be expected only when cancer cells express antigens that are not usually expressed in normal adult cells."
This is what the RNA darts accomplish by introducing genetic material mimicking that of a virus. Immune responses that would normally go unprovoked by cancer cells—or in some cases even support those cells—are tricked into thinking there's a virus on the move.
Recruiting a patient's own immune system into fighting cancer is not in itself a new idea. But it is one that's proven difficult for a variety of reasons. Targeting and activating immune cells in just the right way isn't a simple matter and prior attempts have required fairly complex techniques involving fine-tuning antigens and antibodies and, in many cases, custom engineering dendritic cells (which function as immune system messengers).
The method described here gets around a lot of that mess by using electric charge as a targeting mechanism. Rather than introducing some cultured cell or complicated nanoparticle, this is just RNA stashed within a fatty acid membrane, similar to a cell membrane. (The combined package is known as RNA-LPX.) By tweaking the relative proportions of RNA and fatty acids, the researchers were able to produce particles with a slight negative charge. This charge helps direct the particles to dendritic cells located in the spleen and other lymphoid tissues (bone marrow, lymph nodes).
The dendritic cells then take in the RNA and produce cancer-specific antigens in response. These antigens in turn prompt a T-cell response directed against progressive tumors in the body—tumors that might otherwise be ignored or otherwise be treated as normal by the immune system.
"[The] stimulation of strong immune responses against self-antigens observed in the first cohort of patients supports the preclinically identified mode of action and strong potency of this approach in the clinical setting," the study concludes. "RNA-LPX vaccines are fast and inexpensive to produce, and virtually any tumour antigen can be encoded by RNA. Thus, the nanoparticulate RNA immunotherapy approach introduced here may be regarded as a universally applicable novel vaccine class for cancer immunotherapy."
As one might surmise given the tiny subject population (of mice and three human patients), this is only in the very preliminary stages and many more studies will be required. At the very least, the great big old problem of cancer itself looks a bit more solvable than it did last week.