Overall survival rates for patients with melanoma that has spread to the brain are under six months. In such advanced cancer patients, systemic drugs given intravenously and orally do not effectively target brain metastases.

Immunotherapies, which harness the immune system's power to attack cancer cells, have the potential to improve metastatic melanoma treatment. However, in early clinical immunotherapy studies, the prognosis for most patients remained poor.

Seeking to develop new immunotherapies that could be delivered locally to tumors, the researchers hypothesized that using stem cells to deliver cancer-fighting viruses would amplify the amount of virus released and ensure that the virus would not be degraded by circulating antibodies before impacting the cancer cells.

The team designed a twin stem cell model to maximize the therapy's impact on cancer cells that have spread to a part of the brain called the leptomeninges. One stem cell releases a cancer-killing, or oncolytic, virus -- a strategy previously shown to hold promise in reducing tumor growth. However, oncolytic viruses also destroy the cells that release it, making this an unsustainable therapeutic option on its own.

Therefore, the scientists used CRISPR/Cas9 gene editing to create a second stem cell that would not be targeted by the oncolytic virus. This stem cell releases proteins called immunomodulators that fortify the immune system to help fight off cancer.

The twin stem cells can be delivered via intrathecal injection, a technique currently used in other disease treatments. Unlike some immunotherapies, the stem cells do not require repeated administration.

In preclinical studies, the researchers found that the therapy activated immune responses in mice designed to exhibit a condition that mimics human melanoma with leptomeningeal metastasis. The immune responses in the mice were similar to human immune responses, improving the chances of the therapy succeeding in a phase I trial.

The researchers believe this approach can also be used in other cancers, including lung and breast cancers, which metastasize to the brain. They are currently designing similar treatments for such cancers.

"A number of biological therapies that look promising often fail in phase I or phase II clinical trials, in part because the preclinical models do not authentically replicate clinical settings. We realized that if we did not fix this piece of the puzzle, we would always be playing catch-up," corresponding author Khalid Shah, Harvard Medical School professor, said in a statement. "I don't think we've been at a point in the last 20 years where we have been as close to curing metastases in the brain as we are now."

Disclosures: Khalid Shah owns equity in and is on the board of directors of Amasa Therapeutics, a company developing stem cell-based therapies for cancer. He has filed a patent application entitled "Gene editing and engineering stem cell for drug delivery."

Swiss researchers awaken dormant cells to fight melanoma
Researchers from the University of Geneva and the University Hospitals of Geneva have identified a drug-targetable mechanism whose blockage reduces metastatic...

Cancer vaccine eliminates tumors, prevents recurrence in mice with metastatic melanoma
Tufts University School of Engineering researchers have come up with a method of targeting cancer in mice using an mRNA-based vaccine that is delivered...

Single-cell analyses shed light on drug resistance of melanoma brain metastases
Using single-cell genetic analyses of frozen brain samples, Columbia University researchers have uncovered evidence of how melanoma brain metastases evade...

RNA molecules identified as potential ‘common driver’ of cancer progression
Moffitt Cancer Center researchers have challenged the widely held view that protein structure and function are the key drivers of cancer development....

Study finds cancer cells gravitate toward mechanical ‘sweet spot’ environments
An international team of researchers, led by University of Minnesota Twin Cities engineers, has discovered that cancer cells invade the body based on...

Study of T-cell behavior predicts therapeutic differences in cancer outcomes
Researchers at Weill Cornell Medicine have published a study in Cancer Cell revealing a novel insight on the role of T cells in cancer therapies....

Lower lung cancer, melanoma mortality drives down cancer deaths
Declines in mortality due to lung cancer and melanoma have contributed to decreased overall cancer death rates in the U.S. among both men and women and...

Therapeutic Solutions files patent for stem cell-based cancer vaccine
Therapeutic Solutions International has filed a patent for data that show a positive combined effect between its tumor blood vessel killing vaccine and...