Only two kinds of vaccines that can prevent certain types of human cancers are available. One is the human papillomavirus (HPV) vaccine that protects against genital cancer, while another is the hepatitis B (HBV) vaccine, which prevents hepatitis B infection that can lead to liver cancer.
There are also cancer-treatment (therapeutic) vaccines that offer a type of immunotherapy to boost the body’s natural defenses to fight malignant tumors that already exist; these may prevent cancer from returning, stop a tumor from growing or spreading or kill any cancer cells remaining in the body after other treatments have ended.
But vaccines that prevent cancer from developing are still rare. There is good news, however, from Tel Aviv University researchers who have developed in mouse models a vaccine – based on nanoparticles – that has so far proven effective in preventing the development of melanoma – the most aggressive type of skin cancer.
Prof. Ronit Satchi-Fainaro, head of the university’s physiology and pharmacology department and head of the laboratory for cancer research and nanomedicine at TAU’s Sackler Faculty of Medicine directed the research, carried out by Dr. Anna Scomparin of Prof. Satchi-Fainaro’s TAU lab, who worked together with Prof. Helena Florindo of the University of Lisbon while on sabbatical at the Satchi-Fainaro lab, and post-doctoral fellow Dr. João Conniot. The results have just been published in Nature Nanotechnology.
The nano-vaccine for melanoma is based on an innovative approach in mouse models and in treating primary tumors and metastases that result from melanoma.
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 surgery, chemotherapy, radiation therapy and immunotherapy; but the vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” noted Satchi-Fainaro. “In our study, we have shown 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 that had melanoma.
“The nanoparticles acted just like known vaccines for viral-borne diseases,” explained. Satchi-Fainaro. “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,” continued 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 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,” concluded 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.”
This project was funded by EuroNanoMed-II, the Health Ministry in Jerusalem, the Portuguese Foundation for Science and Technology (FCT), the Israel Science Foundation (ISF), the European Research Council (ERC) Consolidator and Advanced Awards, the Saban Family Foundation Melanoma Research Alliance (MRA) Team Science Award and the Israel Cancer Research Fund (ICRF).