Researchers Develop Nanoparticle-Based Vaccine for Skin Cancer

Nano-particles developed by scientists at Tel Aviv University have proven effective to prevent and treat melanoma.

 

While scientists have made great strides over the years to treat cancer, a vaccine for the disease—which comes in many forms and with many complexities–has yet to be discovered.

Researchers at Tel Aviv University have made a breakthrough in this endeavor with the development of a nano-vaccine for the most aggressive type of melanoma—skin cancer. The vaccine—based on a novel nanoparticle—already has shown effective in preventing the development of melanoma in mice as well as in treating the initial tumors that result from the disease, researchers said.

Researchers have developed a new nano-vaccine for melanoma, the most aggressive type of skin cancer. The vaccine is the first of its kind for cancer and paves the way for promising new prevention and treatment methods for the disease, researchers said. (Image source: Tel Aviv University)

Melanoma develops in the skin cells that produce melanin or skin pigment, but then can metastasize quickly into the brain and other organs. It currently is treated in a number of ways, including chemotherapy, radiation therapy, and immunotherapy.

All of these methods attack the disease after the fact; so far, no treatment has emerged to prevent or delay its growth in the first place, Professor Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology at Tel Aviv University, said in a press statement.

“The vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” said Satchi-Fainaro, who also is head of the Laboratory for Cancer Research and Nanomedicine at the university’s Sackler Faculty of Medicine. “In our study, we have shown for the first time that it is possible to produce an effective nano-vaccine against melanoma and to sensitize the immune system to immunotherapies.”

A New Approach

Nanoparticles about 170 nanometers in size are key to the approach researchers took to developing their novel vaccine. They packed two peptides—or short chains of amino acids—into each particle, which are made of a biodegradable polymer. Peptides are present in melanoma cells.

To test their vaccine, researchers injected the nano-particles into a mouse with melanoma to test its effectiveness. What they found is that the nanoparticles acted similarly to existing vaccines for viruses, which long have proved effective against viral-borne diseases, Satchi-Fainaro said.

“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 said in the statement. “This meant that, from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body.”

Researchers published a study on their work in the journal Nature Nanotechnology.

Successful Prevention and Treatment

Satchi-Fainaro’s team focused on three different conditions to determine the nano-vaccine’s effectiveness. The first was to see if it would prevent the growth of the disease if melanoma cells were injected into mice, which it did, she said.

Researchers also used the nano-vaccine to treat a primary melanoma tumor in combination with immunotherapy treatments, they said. The treatment delayed the progression of the disease and significantly extended the lives of the mice in this study, researchers said.

Finally, the researchers gauged the nano-vaccine’s effectiveness in treating brain metastases, which are associated with melanoma, using tissue from patients with these metastases. The vaccine showed it could also be a successful treatment in this case, paving the way for “effective treatment of melanoma, even in the most advanced stages of the disease,” Satchi-Fainaro said in the statement.

The team plans to continue its work to develop nano-particles to vaccinate people not only against melanoma, but potentially against other forms of cancer as well, she added.

 

Scientists develop novel nano-vaccine for melanoma

Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Credit: Wikipedia/CC BY-SA 3.0

Researchers at Tel Aviv University have developed a novel nano-vaccine for melanoma, the most aggressive type of skin cancer. Their innovative approach has so far proven effective in preventing the development of melanoma in mouse models and in treating primary tumors and metastases that result from melanoma.

The focus of the research is on a nanoparticle that serves as the basis for the new vaccine. The study was led by Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology and head of the Laboratory for Cancer Research and Nanomedicine at TAU’s Sackler Faculty of Medicine, and Prof. Helena Florindo of the University of Lisbon while on sabbatical at the Satchi-Fainaro lab at TAU; it was conducted by Dr. Anna Scomparin of Prof. Satchi-Fainaro’s TAU lab, and postdoctoral fellow Dr. João Conniot. The results were published on August 5 in Nature Nanotechnology.

Melanoma develops in the skin cells that produce melanin or skin pigment. “The war against cancer in general, and melanoma in particular, has advanced over the years through a variety of treatment modalities, such as chemotherapy, radiation therapy and immunotherapy; but the vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” says Prof. Satchi-Fainaro. “In our study, we have shown for the first time that it is possible to produce an effective nano-vaccine against melanoma and to sensitize the immune system to immunotherapies.”

The researchers harnessed tiny particles, about 170 nanometers in size, made of a biodegradable polymer. Within each particle, they “packed” two peptides—short chains of amino acids, which are expressed in melanoma cells. They then injected the nanoparticles (or “nano-vaccines”) into a mouse model bearing melanoma.

“The nanoparticles acted just like known vaccines for viral-borne diseases,” Prof. Satchi-Fainaro explains. “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. This meant that, from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body.”

The researchers then examined the effectiveness of the vaccine under three different conditions.

First, the vaccine proved to have prophylactic effects. The vaccine was injected into healthy mice, and an injection of melanoma cells followed. “The result was that the mice did not get sick, meaning that the vaccine prevented the disease,” says Prof. Satchi-Fainaro.

Second, the nanoparticle was used to treat a primary tumor: A combination of the innovative vaccine and immunotherapy treatments was tested on melanoma model mice. The synergistic treatment significantly delayed the progression of the disease and greatly extended the lives of all treated mice.

Finally, the researchers validated their approach on tissues taken from patients with melanoma brain metastases. This suggested that the nano-vaccine can be used to treat brain metastases as well. Mouse models with late-stage melanoma brain metastases had already been established following excision of the primary melanoma lesion, mimicking the clinical setting. Research on image-guided surgery of primary melanoma using smart probes was published last year by Prof. Satchi-Fainaro’s lab.

“Our research opens the door to a completely new approach—the vaccine approach—for effective treatment of melanoma, even in the most advanced stages of the disease,” concludes Prof. Satchi-Fainaro. “We believe that our platform may also be suitable for other types of cancer and that our work is a solid foundation for the development of other cancer nano-vaccines.”

More information: Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators, Nature Nanotechnology(2019). DOI: 10.1038/s41565-019-0512-0 , https://nature.com/articles/s41565-019-0512-0

Journal information: Nature Nanotechnology

Provided by Tel Aviv University