The Jonsson Comprehensive Cancer Center on the campus of the University of California, Los Angeles (UCLA) houses a research group that created tumor-seeking, cancer-killing immune cells. This same group used positron emission tomography (PET) to observe these engineered cells in real time as they traveled throughout the body to locate and attack dangerous skin tumors called melanomas. The immune cells were made by means of genetic engineering. They used an HIV-like virus as the means to endow these immune cells with the genes for T-cell receptors that caused the lymphocytes to become specific killers of cancerous cells. They also gave the engineered lymphocytes with a “reporter gene” that allows scientists to track them during a PET scan. After they were injected into the bloodstream, the genetically engineered lymphocytes made their way to the lungs and lymph nodes, and then specifically homed in on the tumors wherever they were located in the body.
Dr. Antoni Ribas, an associate professor of hematology–oncology and a researcher at UCLA’s Jonsson Comprehensive Cancer Center put it this way: “We’re trying to genetically engineer the immune system to become a cancer killer and then image how the immune system operates at the same time. We knew this approach of arming the lymphocytes with T-cell receptors showed significant anti-tumor activity based on studies in humans. Now, by tracking the immune system’s reaction to cancer and imaging it in real time, we can project how the same process that succeeded in mice might behave in people.”
“The novelty of our work is that we were able to pack together the cancer-specific T-cell receptor and the PET reporter genes in a single vector and use it in mice with an intact immune system that closely resembles what we would see in real patients,” said Dr. Richard Koya, an assistant professor of surgical oncology at the David Geffen School of Medicine at UCLA and first author of the study. “We were also gladly surprised to see the targeted tumors literally melt away and disappear, underscoring the power of the combined approach of immune and gene therapy to control cancer.”
Typically, the immune system fails to recognize cancer cells in the body as foreign entities. By inserting an antigen-specific T-cell receptor that was engineered to seek out a tumor antigen on the surface of melanoma cells, the researchers effectively “uncloaked” the malignant cells and designated them as the deadly invaders they are. When viewed with a PET scan, these genetically engineered T cells appeared to seek out and attack the cancer. This technique, in fact, this technique might provide oncologists with better ways to fight malignancies and monitor responses to therapy in cancer patients.
In this study, after the engineered T cells found the tumors and began to fight them within two the three days after their injection into the bloodstream of the mice. These mice were routinely examined with PET scans for ten days to ensure the lymphocytes were indeed killing the cancer. Such a process would almost certainly take longer in people. Some 1 million genetically engineered lymphocytes were created and injected into a mouse in this study, but it would take about one billion tumor-seeking cells to fight cancer in humans.
Ribas and his team are working now on inventing ways to insert T-cell receptor and reporter genes into the lymphocytes in a way that is safe for use in humans. Human studies of the process could conceivably begin in about a year, according to Ribas. This study appears July 12 in the early online edition of the journal Proceedings of the National Academy of Sciences.