Soon a Vaccine to Prevent Melanoma

A personalized “cancer vaccine” may help keep a deadly form of skin cancer from growing for years, a small new study in humans suggests. Unlike vaccines that prevent infections, such as measles and influenza, cancer vaccines are a form of immunotherapy that take down cancer cells that already exist. The vaccines train immune cells, called T cells, to better recognize cancer and target it for destruction, while sparing healthy cells in the body. For example, the new experimental vaccine works by training T cells to spot specific proteins on melanoma cells, a type of skin cancer. In the study, scientists found that the T cells continue to “remember” these proteins for at least four years after the vaccination — and they even learn to recognize more melanoma-related proteins over time.

The only way that could have happened is if there was actually killing of the tumor cells. And presumably it was the T cells induced by the vaccine that did that killing,” said study author Dr. Catherine Wu, a physician-scientist with the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. That’s because, once killed, tumor cells fall apart and spill their contents; T cells then swoop in to examine these remains and log that information away for future attacks, Wu said.

While the results are promising, the new study only included eight patients, and more trials need to be conducted to pin down exactly how effective the vaccine is, she added. But as of now, the limited data hint that the vaccine triggers a persistent immune response and can help keep cancer under control, especially when combined with other immunotherapies, the authors noted. The new study, published Jan. 21 in the journal Nature Medicine, included patients with advanced melanoma who had recently undergone surgery for the cancer. The researchers took samples of the patients’ removed tumors and used them to craft personalized vaccines for each of the eight participants.


The Rising Of Gene Therapy

After false starts, drugs that manipulate the code of life are finally changing lives. The idea for gene therapy—a type of DNA-based medicine that inserts a healthy gene into cells to replace a mutated, disease-causing variant—was first published in 1972. After decades of disputed results, treatment failures and some deaths in experimental trials, the first gene therapy drug, for a type of skin cancer, was approved in China in 2003. The rest of the world was not easily convinced of the benefits, however, and it was not until 2017 that the U.S. approved one of these medicines. Since then, the pace of approvals has accelerated quickly. At least nine gene therapies have been approved for certain kinds of cancer, some viral infections and a few inherited disorders. A related drug type interferes with faulty genes by using stretches of DNA or RNA to hinder their workings. After nearly half a century, the concept of genetic medicine has become a reality.

These treatments use a harmless virus to carry a good gene into cells, where the virus inserts it into the existing genome, canceling the effects of harmful mutations in another gene.

GENDICINE: China’s regulatory agency approved the world’s first commercially available gene therapy in 2003 to treat head and neck squamous cell carcinoma, a form of skin cancer. Gendicine is a virus engineered to carry a gene that has instructions for making a tumor-fighting protein. The virus introduces the gene into tumor cells, causing them to increase the expression of tumor-suppressing genes and immune response factors.The drug is still awaiting FDA approval.

GLYBERA: The first gene therapy to be approved in the European Union treated lipoprotein lipase deficiency (LPLD), a rare inherited disorder that can cause severe pancreatitis. The drug inserted the gene for lipoprotein lipase into muscle cells. But because LPLD occurs in so few patients, the drug was unprofitable. By 2017 its manufacturer declined to renew its marketing authorization; Glybera is no longer on the market.

IMLYGIC: The drug was approved in China, the U.S. and the E.U. to treat melanoma in patients who have recurring skin lesions following initial surgery. Imlygic is a modified genetic therapy inserted directly into tumors with a viral vector, where the gene replicates and produces a protein that stimulates an immune response to kill cancer cells.

KYMRIAH: Developed for patients with B cell lymphoblastic leukemia, a type of cancer that affects white blood cells in children and young adults, Kymriah was approved by the FDA in 2017 and the E.U. in 2018. It works by introducing a new gene into a patient’s own T cells that enables them to find and kill cancer cells.

LUXTURNA: The drug was approved by the FDA in 2017 and in the E.U. in 2018 to treat patients with a rare form of inherited blindness called biallelic RPE65 mutation-associated retinal dystrophy. The disease affects between 1,000 and 2,000 patients in the U.S. who have a mutation in both copies of a particular gene, RPE65. Luxturna delivers a normal copy of RPE65 to patients’ retinal cells, allowing them to make a protein necessary for converting light to electrical signals and restoring their vision.

STRIMVELIS: About 15 patients are diagnosed in Europe every year with severe immunodeficiency from a rare inherited condition called adenosine deaminase deficiency (ADA-SCID). These patients’ bodies cannot make the ADA enzyme, which is vital for healthy white blood cells. Strimvelis, approved in the E.U. in 2016, works by introducing the gene responsible for producing ADA into stem cells taken from the patient’s own marrow. The cells are then reintroduced into the patient’s bloodstream, where they are transported to the bone marrow and begin producing normal white blood cells that can produce ADA.

YESCARTA: Developed to treat a cancer called large B cell lymphoma, Yescarta was approved by the FDA in 2017 and in the E.U. in 2018. It is in clinical trials in China. Large B cell lymphoma affects white blood cells called lymphocytes. The treatment, part of an approach known as CAR-T cell therapy, uses a virus to insert a gene that codes for proteins called chimeric antigen receptors (CARs) into a patient’s T cells. When these cells are reintroduced into the patient’s body, the CARs allow them to attach to and kill cancer cells in the bloodstream.

ZOLGENSMA: In May 2019 the FDA approved Zolgensma for children younger than two years with spinal muscular atrophy, a neuromuscular disorder that affects about one in 10,000 people worldwide. It is one of the leading genetic

causes of infant mortality. Zolgensma delivers a healthy copy of the human SMN gene to a patient’s motor neurons in a single treatment.

ZYNTEGLO: Granted approval in the E.U. in May 2019, Zynteglo treats a blood disorder called beta thalassemia that reduces a patient’s ability to produce hemoglobin, the protein in red blood cells that contains iron, leading to life-threatening anemia. The therapy has been approved for individuals 12 years and older who require regular blood transfusions. It employs a virus to introduce healthy copies of the gene for making hemoglobin into stem cells taken from the patient.The cells are then reintroduced into the bloodstream and transported to the bone marrow, where they begin producing healthy red blood cells that can manufacture hemoglobin.

The approach called ‘Gene Interference‘ uses a synthetic strand of RNA or DNA (called an oligonucleotide) that, when introduced into a patient’s cell, can attach to a specific gene or its messenger molecules, effectively inactivating them. Some treatments use an antisense method, named for one DNA strand, and others rely on small interfering RNA strands, which stop instruction molecules that go from the gene to the cell’s protein factories.


Injection Of Nanoparticle Effective Against Melanoma

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. 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 results were published recently in Nature Nanotechnology.