University of Massachusetts Medical School (UMMS) researchers developed a new technique using near-infrared light that was able to stimulate immune cells in melanoma mice models, and which could result in a more selective and less invasive way of treating melanoma and, possibly, other cancers. The study, “Near-infrared photoactivatable control of Ca2+signaling and optogenetic immunomodulation,” was published in the journal e-LIFE.
From the therapeutic viewpoint, a number of immunotherapy agents, such as interleukin-2 (IL-2) or interferon, are currently available to treat melanoma tumors but show limited success. These agents also are prone to causing systemwide side effects, as they do not target only melanoma cells.
A novel method known as optogenetics, a combination of new optical technology and genetic advances, interests the neuroscience community due to its capacity to map and decipher neuronal circuits in live animals. The technique is based on the stimulation of neurons by means of light — because neurons contain light receptor proteins, they respond to pulses of individual colors. However, since cells have different methods of communication, optogenetics is difficult to adapt, especially for cells located deep in the body where light penetration becomes challenging.
To overcome this problem, UMMS researchers used the flow of calcium ions as a novel approach to stimulate immune cells using up-conversion nanoparticles. When attached to cells, these nanoparticles convert near-infrared light, able to more deeply penetrate the skin, to visible blue light. This, in turn, activates the light receptor proteins that regulate the flow of calcium into cells.
Researchers genetically engineered blue light-sensitive calcium channels controlling protein cells to facilitate the process. Exposure to blue light activates calcium ion channels within cells, which in turn communicate with immune cells, called T-cells, that initiate the fight against melanoma cells.
The method was tested in melanoma mice models using both nanoparticles and genetically engineered immune cells. “When we exposed a near-infrared laser beam to these animal models injected with both the nanoparticle and the genetically engineered immune cells, this caused calcium channels on the dendritic cells to open and we saw a corresponding increase in the number of T-cells that were activated,” Gang Han, PhD, the study’s author and an assistant professor of biochemistry & molecular pharmacology, said in a news release.
“More importantly,” said Dr. Han, “we saw significantly suppressed tumor growth and reduced tumor volume in these animals. This suggests that the activated dendritic cells were successfully programming T-cells to attack the tumor.”
This method could lead to the development of novel cancer immunotherapies that are less invasive, more controlled, and more with limited side effects than currently available therapies. “This is the first time anybody has used optogenetic techniques to stimulate the immune system, much less to fight cancer cells,” Dr. Han said. “The advantage an optogenetic approach has over other immunotherapies, which typically activate global immune responses, is that we now have the tools to closely monitor the dose and location of the treatment to mitigate potential side effects to healthy tissues.”
“Any cell that used calcium to perform its task could potentially be activated using this newly developed technology,” Dr. Han concluded. “The flexibility of this system means it can be adapted to explore other cellular processes while minimally interfering with other physiological or biological functions.”
