Sept. 12 (UPI) — Individualized treatment for melanoma would reduce the number of cancer cells, based on a study in lab dishes and animals.
Researchers at the Weizmann Institute of Science in Israel envision the development of personalized drugs because almost all neo-antigens detected in patients are unique to the particular cancerous tissue. They published their findings Wednesday in the journal Cancer Discovery.
“This would be the ultimate ‘personalized’ cancer therapy — a new drug is created for every patient,” Dr. Yardena Samuels, a researcher in the Institute’s Molecular Cell Biology Department, said in a press release.
This year, an estimated 178,560 cases of melanoma will be diagnosed in the United States, according to the Skin Cancer Foundation. An estimated 9,320 people in the United States die yearly from the cancer.
Melanoma, the most lethal form of skin cancer, is usually curable if caught early.
Immunotherapies now involve two methods: administering antibodies to unlock the natural immune T cells kill cancer cells and growing and reactivating these T cells outside the body and returning them as “weaponized.”
“But none of this will kill the cancer if the immune cells do not recognize the ‘signposts’ that mark cancer cells as foreign,” Samuels said.
The genes’ signposts are mutated peptides known as neo-antigens on the cancer cells’ outer membranes.
Although these particular peptides can be used to develop personalized cancer vaccines based on neo-antigen profiles, they are difficult to determine in melanoma and some other cancers.
A protein complex called HLA has thousands of versions even without the addition of cancerous mutations.
Instead of relying on algorithms, the researchers removed the peptides from the melanoma cells’ HLA complex and checked their interactions with T cells.
“We discovered that tumors present many fewer neo-antigens than we expected,” Samuels said. “Our neo-antigen and corresponding T-cell-identification strategies were so robust, our neo-antigen-specific T cells killed 90 percent of their target melanoma cells both on plates and in mice.”
Someneo-antigens had not even shown up in algorithm studies.
With some patients, they obtained multiple samples, including determining whether the same neo-antigens were part of secondary tumors after it had spread to other organs.
“This is the first time that HLA peptide studies of multiple metastases derived from the same patient have ever been performed,” Ph.D. student Shelly Kalaora said. “The significant similarity between the various HLA-peptidomes has strong implications for the process of choosing neo-antigens for patient treatment, showing that it is clearly essential not only to identify the immunogenic peptides presented on the cancer cells, but to select the ones that are common to the patient’s metastases.”
In further research, they extracted natural T cells from 14 of the patients and found those that most strongly react with the neo-antigens. Then, they sequenced the genomes of these cells, grew them and tested them in animal models with the patients’ tumor cells.
In lab dish and animal studies, the response of the T cells they identified was highly effective in fighting the cancer.