A promising bacterial vaccine prepared by Columbia researchers may mark a revolution in cancer immunotherapy. The new vaccine uses probiotic bacteria to educate the immune system to recognize and attack cancer cells, thereby opening the door to a new class of cancer vaccines that exploit bacteria’s natural predilection to target tumors.
In tests on mouse models of colorectal cancer and melanoma, the bacterial vaccine triggered an immune response that targeted not only the primary tumors but also their metastases. Sometimes the tumors vanished altogether, with healthy tissue remaining unscathed. Nature has now published these remarkable findings.
The bacterial vaccine also outperformed classic peptide-based cancer vaccines, which numerous clinical trials have tried with limited success.“Our system has the unique ability to activate all arms of the immune system, inducing a strong anti-tumor response, especially in challenging solid tumor models,” said Andrew Redenti, an MD/PhD student at Columbia University.
The bacterial vaccine customizes itself for each patient. Since cancer cells carry different genetic mutations, the bacteria target only the specific mutation of that patient. That means it could prompt the patient’s body to recognize cancer cells and attack them without actually touching the healthy cells.
Nicholas Arpaia, PhD – lead researcher in the study, said: “Every cancer is different. By programming bacteria to target cancer-specific mutations, we can engineer more effective therapies that work with the body’s immune system to fight the cancer.”
Scientists create this bacterial vaccine using a probiotic type of E. coli. They engineer these bacteria in multiple ways to control how they expose their antigens to the immune system. The engineered bacteria carry protein targets, called neoantigens, specific to the cancer being treated. These neoantigens instruct the immune system to attack only the tumor cells expressing these proteins and leave healthy cells alone.
The bacteria also overcome some of the immunosuppressive mechanisms that tumors use to evade the immune system. The researchers have also genetically engineered the bacteria in such a way that they cannot evade the immune attacks. If the bacteria do not find the tumor, then the immune system can easily recognize and eliminate them.
It tested a vaccine in mice, which recruited into battle a broad range of immune cells that attack cancer-not only effectively but without letting the immune system suppress such attacks. When researchers gave an advanced bacterial vaccine to mice before tumors started to form, the vaccine hindered cancer growth. It also blocked tumor regrowth in mice that had already been cured, suggesting that the vaccine might prevent patients already in remission from experiencing recurrence.
It begins by sequencing the specific cancer in a patient to identify neoantigens that are unique to the tumor. And engineer bacteria to manufacture them among other stimulative factors. After infusion, the bacteria target the tumor to make those neoantigens with other stimulative factors to enhance the immune fight against it.
Researchers believe this approach may succeed where earlier cancer vaccines have failed. Unlike previous methods, this vaccine can target the tumor environment directly and stimulate the immune response with much more effectiveness. Hence, it has opened a new hope for it’s treatment.
“This platform delivers a much higher concentration of medicine directly to the tumor. It avoids the side effects of systemic delivery,” said Arpaia. The researchers are hopeful for better outcomes with this approach in the future for cancer patients.
ANI