A new anti-cancer vaccine developed by researchers at RIKEN Center for Integrative Medical Sciences in Japan has been shown to mobilize innate immune response, and more specific adaptive response in animal tests. The strategy, which allows the immune system to keep memories and attack new tumor cells as they form, is more efficient than commonly used immunotherapies.
The study, “Systemic DC Activation Modulates the Tumor Microenvironment and Shapes the Long-Lived Tumor-Specific Memory Mediated by CD8+ T Cells,” was published in Cancer Research.
“Cancer cells have different sensitivities to the innate or adaptive response, so it is important to target both in order to eradicate it. We have developed a special type of modified cell, called aAVC, which we found can do this,” Shin-ichiro Fujii, the study’s lead author said in a press release.
Although strategies that boost the immune system are included in several cancer therapies, efficiency is often reduced because of the inability of immune cells to enter the immunosuppressive tumor microenvironment. The researchers suggest that combining multiple therapies could be beneficial, because immune escape may be better avoided when different immune responses are activated.
The aAVC cells, which are not isolated from the patient, are modified to present a ligand that activates natural killer T (NKT)-cells and a protein expressed in cancer cells. When NKT cells become activated, they can establish contact and mature dendritic cells (DCs), which coordinate the activation of the immune memory, allowing the immune system to remember a threat and respond to it many years later.
The researchers tested aAVCs in mice that had a virulent form of melanoma expressing the ovalbumin protein (OVA). Vaccinating the animals with aAVC cells, programmed to express the OVA protein at the cell surface, significantly reduced tumor growth and induced necrosis inside the tumor which indicated it was being attacked by CD8 T-cells.
“We were interested in finding a mechanism, and were able to understand that the aAVC treatment led to the development of blood vessels in the tumors that expressed a pair of important adhesion molecules, ICAM-1 and VCAM-1, that are not normally expressed in tumors. This allowed the killer CD8+T cells to penetrate into the tumor,” Fujii said.
Animals given aAVC vaccination were able to eliminate melanoma cells injected again a year later, which Fujii said proves success.
“Our therapy with aAVC is promising because typical immunotherapies have to be tailor-made with the patient’s own cells,” Fujii said. “In our case we use foreign cells, so they can be made with a stable quality. Because we found that our treatment can lead to the maturation of dendritic cells, immunotherapy can move to local treatment, to more systemic treatment based on immune memory.”
