• Researchers have developed a new vaccine that shows promise in overriding an immune escape mechanism in cancerous tumors.
• They found that the vaccine offers protection against cancerous tumors in mouse and primate cancer models.
• They plan to enter the vaccine into clinical trials next year.

Developing cancer vaccines have been an essential part of cancer research for almost three decades.

Many forms of cancer vaccines are under research, including those that target proteins expressed across multiple cancer types, and those that are personalized according to individual tumor mutations.

While existing vaccines can induce an immune response in blood, tumors often dodge this response via an immune escape mechanism.

Targeting this mechanism may help researchers improve cancer vaccine efficacy.

In a recent study, researchers developed a new cancer vaccine that targets this immune escape mechanism and increases immune antibody levels.

The study was published in Nature.

How the vaccine works

Dr. Santosh Kesari, director of neuro-oncology at Providence Saint John’s Health Center, chair of the Department of Translational Neurosciences and Neurotherapeutics at Saint John’s Cancer Institute in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California, who was not involved in the study, explained to Medical News Today how the vaccine worked.

“This new approach [t]argets this resistance mechanism by making a vaccine to a general protein that is over expressed (a stress signal) in cancers but is rapidly removed by the cancer before the immune system detects it.”
— Dr. Santosh Kesari

“The new vaccine approach prevents the cancer cell from removing this cancer-specific protein and thus allows a coordinated immune attack on the cancer by both T- cells and natural killer (NK) cells,” he said.

The researchers designed the new vaccine to target MICA and MICB stress proteins, which sit on the surface of cancer cells.

While immune cells in the body, known as T cells and NK cells, typically bind to these stress proteins in an attempt to kill cancerous cells, tumor cells can evade their attack by slicing MICA/B and shedding them.

The new vaccine prevents this slicing and thus increases stress protein expression and the activation of a dual attack from T cells and NK cells.

Tests on mice, monkeys

To begin, the researchers administered their new vaccine to mouse models of cancer that were modified to express human MICA/B proteins.

They found that the vaccines increased antibody levels in the mice, and demonstrated anti-tumor effects.

The researchers then evaluated immunological memory from the vaccine. Four months after initial immunization, the researchers exposed mice to tumor cells and found that they remained fully protected.

The researchers also found that introducing small quantities of blood from vaccinated mice inhibited cell-surface MICA/B protein shedding on human and mouse cancer cell lines.

The researchers further noted that the vaccine was effective in controlling multiple tumor types.

The researchers next investigated whether the vaccine could prevent cancer recurrence following surgical tumor removal.

To do so, they immunized mouse models of breast cancer and melanoma with a high chance of recurrence after tumor removal with either the new vaccine or a control vaccine.

They found that, compared to the control vaccine, the new vaccine reduced the number of lung metastases detected in both cancer models more than a month after surgery.

The researchers next tested the vaccine on four rhesus macaques (commonly known as rhesus monkeys). They noted that the vaccine increased antibody levels by 100- 1,000 fold with subsequent booster vaccines.

They reported no clinical side effects or changes in blood chemistry following immunization, which, they wrote, suggests preliminary evidence for vaccine safety.

The researchers concluded that their new vaccine enables protective immunity against tumors with common escape mutations.

Human trials up next

The researchers noted that their results might be limited as they had to express human MICA/B proteins in mouse tumor cells due to differences in mouse and human cellular biology.

When asked what the future holds for research around the vaccine, Dr. Kai W. Wucherpfennig, chair of cancer immunology and virology at the Dana-Farber Cancer Institute and lead author of the study, told MNT that they plan to enter the vaccine into clinical trials next year.

The researchers added that the vaccine might also be used in combination with local radiation therapy as DNA damage enhances MICA/B expression by cancer cells.

“Since this is a broad target to general cancer stress signal, the vaccine may have broad applicability to many cancers and thus could be made to be an off-the-shelf approach,” Dr. Kesari added.

Although the study presents an exciting new approach to cancer vaccines, the results remain preclinical, noted Dr. Kesari.

“[Thus it] will need to be translated in the future in humans by conducting phase I clinical trials in the future to prove out its safety and efficacy,” he concluded.

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