Vaccine Helps Immune System ‘Remember’ Cancer Threats

When activated, a special type of modified cell called aAVC promotes the maturation of dendritic cells, the gatekeepers of immune memory.

AsianScientist (Jul. 1, 2016) – Immunotherapies used in the fight against cancer are often hindered by the inability of the immune cells to enter the tumor and mount an effective response against it.

Now, scientists from the RIKEN Center for Integrative Medical Sciences have developed a vaccine that allows the body to keep immune ‘memories’ and attack new tumor cells as they form.

In the study published in Cancer Research, they showed that the vaccine made it possible for killer CD8+ T cells—important players in the immune response against cancer—to enter the tumor microenvironment and target cancer cells.

“Cancer cells have different sensitivities to the innate or adaptive response, so it is important to target both in order to eradicate them. We have developed a special type of modified cell, called aAVC, which we found can do this,” said Dr. Shin-ichiro Fujii, the lead author of the study.

The aAVC cells are not taken from the subject’s own body but are instead foreign cells. When modified with a natural killer T cell ligand, the modified aAVC cells lead to the activation of natural killer CD8+ T cells.

They also promote the maturation of dendritic cells, which act as coordinators of the innate and acquired response. Dendritic cells are key because they allow the activation of ‘immune memory,’ where the body remembers and responds to a threat even years later.

To test their immunotherapy, the researchers conducted experiments in mice with melanoma that also expressed a model antigen called OVA. The tests showed that aggressive tumors could be shrunken by vaccinating the animals with aAVC cells that were modified to display OVA antigens.

Following the treatment, the tumors in the treated animals were smaller and had a necrotic core—a sign that the tumor was being attacked by the killer CD8+ T cells.

“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, which are not normally expressed in tumors,” Fujii said. “This allowed the killer CD8+ T-cells to penetrate into the tumor.”

In animals that had undergone treatment, cancer cells injected even a year later were eliminated, suggesting that immune memory was activated.

Unlike typical immunotherapies that have to be tailor-made with the patient’s own cells, the benefit of aAVC therapy is that foreign cells can be used instead, Fuijii said.

The article can be found at: Shimizu et al. (2016) Systemic DC Activation Modulates the Tumor Microenvironment and Shapes the Long-lived Tumor-specific Memory Mediated by CD8+ T-Cells.


Source: RIKEN; Photo: Shutterstock.
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