It is estimated that over 87,000 new cases of invasive melanoma will be diagnosed this year. When found early, melanoma can be manageable, but when the disease spreads to other parts of the body, the median survival time is less than a year. Recent data over a novel technique in adoptive immunotherapy is showing promise for melanoma patients, by increasing the lifespan and survivability of trained t cells in the body- without the use of supplemental drugs and interventions that can often cause harmful, sometimes intolerable side effects.
Data from this small Phase I trial, conducted by the Dana Farber Cancer Institute, was recently published in the April 27, 2017 issue of Science Translational Medicine. The results show the longest that injected cells have ever survived in cancer patients without the use of other life-prolonging treatments.
Adoptive immunotherapy requires the collection of T-cells from the patients, and essentially “training” them to fight cancer. To train these cells, they are introduced to protein antigens that are found on tumor cells, as well as a growth stimulator to increase their numbers. Once injected back into the body, these trained cells can then recognize and attack the tumor cells that express these antigens.
Unfortunately, these trained T-cells only last a couple of days before dying off, so other interventions are needed to keep them alive. This can be done by techniques such as depleting a patients’ blood of certain regulatory T-cells, or using interleukin 2, which spurs T-cell growth. However, these T-cell life-extending techniques can cause multiple adverse events, such as nausea, muscle weakness, fever, drops in certain white blood cell levers, as well as more serious ones that might be intolerable for many patients.
Novel Adoptive Immunotherapy Technique
The Dana Farber Cancer institute trial studied 9 patients with advanced melanoma. After 10 weeks on this therapy, seven of the patients had more of the specially trained tumor targeting T-cells than they had beginning the study. One patient showed a complete remission. Another patient had shrinkage of a tumor that had spread to the lungs, and three of the patients had their disease stabilize.
Furthermore, the technique was then investigated in combination with ipibilimumab, a drug that enhanced the cell’s anti-tumor responses. Ipilimumab was given to five patients who had disease progression after the T cell infusions. Results showed that the patients in this trial had sizable increases in the level of anti tumor T cells in the blood. Three of the patients showed long term tumor shrinkage, while two others had their disease stabilize.
This novel treatment involves artificial versions of antigen presenting cells that inform the immune system when cancer is present. These antigen presenting cells are engineering to produce the molecule CD83, which ensures that T cells last long periods of time, as well as Interluekin 15, which essentially trains the T cells to survive. These T-cells, now equipped with the memory of tumor antigens and increased survival, are now powerful tumor-fighting units that are injected back into the body.
It is important to note that the number of trained T-cells present in the tumor site does not necessarily mean an increased survival- since tumor cells often develop resistance to T-cell attack. And while researchers at Dana Farber were actually initially interested in studying the safety of this technique, and whether or not it would increase T-cell life span, they were impressed by the unexpected improvements seen in several of the patients studied. They are hoping to further investigate the technique in combination with other drugs, and are in planning stages for a next set of clinical trials.
Last editorial review: August 10, 2017
Featured Image: Melanoma Courtesy: © 2017. Fotolia. Used with permission.
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