Nanotech Vaccine Aids Melanoma Immunotherapy

Ronit Satchi-Fainaro (Tel Aviv University)

6 Aug. 2019. A vaccine made with nanoscale peptide particles can prevent the occurrence of melanoma in lab mice, and treat the condition when combined with other drugs. Researchers from Tel Aviv University in Israel and University of Lisbon in Portugal report their findings in yesterday’s issue of the journal Nature Nanotechnology (paid subscription required).

A team from the medical school labs of Ronit Satchi-Fainaro in Tel Aviv and Helena Florindo in Lisbon are seeking to improve the outcomes of people with solid tumor cancers treated with checkpoint inhibitors. Immune checkpoint inhibitors treat cancer by blocking proteins keeping the immune system from responding to cancer cells, and allowing tumors to grow unchecked. While promising, checkpoint inhibitors have shown uneven results including low response rates, acquired resistance, and severe side effects, according to the authors.

The researchers developed and tested a vaccine to prevent the occurrence of a specific solid tumor cancer, melanoma, as well as treat the disease. Melanoma is an aggressive type of skin cancer, which while not as common as basal cell and squamous cell skin cancers, is more likely to spread to other parts of the body. If melanoma is caught and treated early, before it spreads or metastasizes, the 5-year survival rate is 98 percent according to American Cancer Society. After the cancer spreads to other parts of the body, however, the 5-year survival rate drops to 23 percent.

The Tel Aviv-Lisbon team designed a vaccine made with nanoscale particles of a biocompatible polymer infused with peptides, short chains of amino acids, from melanoma cells designed to invoke an immune-system response. As a preventive vaccine, the nanoparticles encourage production of T-cells in the immune system, when tested in healthy lab mice, followed by injections of melanoma cells.

“The nanoparticles acted just like known vaccines for viral-borne diseases,” says Satchi-Fainaro in a Tel Aviv University statement. “They stimulated the immune system of the mice, and the immune cells learned to identify and attack cells containing the two peptides, that is, the melanoma cells.” She adds that, “from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body.”

When combined with checkpoint inhibitor drugs and antibodies to promote T-cell production, the nanoparticle vaccine also produced more T-cells, but this combination does not reduce tumor growth in lab mice induced with melanoma. The team also discovered this treatment results in suppressor cells derived from bone marrow infiltrating the tumors, blunting therapeutic effects of the vaccine.

The researchers then added another drug, ibrutinib, a suppressor cell inhibitor to the mix. Ibrutinib is a targeted drug for treating some forms of leukemia and lymphoma, as well as graft-versus-host disease, an immune reaction to some bone-marrow transplants. The results show this vaccine-drug combination reduces and delays progression of primary melanoma tumors in mice, and lengthens their survival times. Tests on samples of brain tissue from patients with melanoma, where the cancer spreads to the brain, suggest the vaccine-drug combination may also be effective with metastatic forms of melanoma.

The researchers believe their nano-vaccine technology can be adapted to other solid tumor cancers. “We believe that our platform may also be suitable for other types of cancer,” notes Satchi-Fainaro, “and that our work is a solid foundation for the development of other cancer nano-vaccines.”

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