A vaccine placed inside a bacterium, which in turn is wrapped in tiny polymer particles, has been used to stimulate rodents' immune systems to attack cancer cells.
Immunotherapy, the use of vaccines to enable the body to recognize and attack tumors, is the subject of extensive research at the moment, with many efforts showing promise using different approaches to the same basic idea.
One of the leading anti-cancer vaccine techniques is to starve tumors by preventing them from forming new blood vessels. Since the rapid growth of cancer needs feeding, squeezing their supply can be an important control mechanism. The oral vaccine NP/SAL primes the immune system to attack the growth factors that many types of cancer use to increase their blood supply.
Getting the vaccine to the tumor remains a significant challenge, however. Bacteria and viruses can be used as delivery vehicles, but they often suffer damage in passing through the body to reach the cancer's location. If the vaccine and carrier can reach the lower gut, they can diffuse through the blood supply to where they are needed, but this involves navigating the obstacles the body creates to keep pathogens from the digestive system.
A new paper in Nano Letters notes, “Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process.”
As co-author Yuan Ping of Nanyang Technological University, Singapore, told Phys.org, “Only a few [methods so far investigated] could successfully surmount substantial hurdles to oral vaccine development.”
Ping and colleagues coated Salmonella (which had first been modified to remove most of the poisonous effects) with positively charged polymers that attach to the walls of the negatively charged bacteria.
The coating offers the Salmonella protection against the extreme acidity of the stomach. Moreover, the polymers provide a defense mechanism against phagosomes, cellular containers in which white blood cells encase foreign objects to prevent them from damaging the body. The polymers draw protons from the phagosomes, causing them to swell and break.
Credit: Hu, et al. ©2015 American Chemical Society. Nanoparticles shield bacteria so they can deliver their anti-cancer payload.
When the team gave mice an oral NP/SAL vaccine using polymer-coated Salmonella, they found that 60% showed no tumor growth over the course of a 35 day trial. The mice also showed no ill effects from the treatment.
"Immunotherapeutic agents have provided limited evidence of clinical success until recent advances in understanding how cancer cells escape recognition and attack by the immune system," Ping told Phys.org.
“Because there are quite a few bacteria choices besides Salmonella, and also a large number of functional nanoparticles available,” Ping says, “we expect to engineer different types of vaccines that are precisely tailored for more specific applications. The adaptable and versatile properties of this vaccine design strategy opens up new possibilities for treating a wide spectrum of immunological diseases in the dawning era of personalized nanomedicine." Widespread application of the delivery vehicles could be available in as little as 3-5 years.