UCLA Creates Lymphocytes That Stalk Melanoma

July 13, 2010

Like satellites tracking an invading force, a PET scanner at UCLA follows a battalion of tumor-seeking lymphocytes stalking melanoma tumors. Radioactive reporter genes, embedded in the lymphocytes, show the real-time location of these immune cells, genetically engineered to recognize antigens on the surface of the tumor cells.

Like satellites tracking an invading force, a PET scanner at UCLA follows a battalion of tumor-seeking lymphocytes stalking melanoma tumors. Radioactive reporter genes, embedded in the lymphocytes, show the real-time location of these immune cells, genetically engineered to recognize antigens on the surface of the tumor cells.

It would be much better if that battlefield were in patients and, one day, it might be. But for now the UCLA team at Jonsson Comprehensive Cancer Center is working out the logistics for battling melanoma in mice.

“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 [will] behave in people,” said Dr. Antoni Ribas, a UCLA associate professor of hematology/oncology and senior author of the study, whose data were published July 12 in the early online edition of the journal Proceedings of the National Academy of Sciences.

The work is unlike any done before. The researchers were able to pack together the cancer-specific T-cell receptor and the radioactively labeled reporter genes in a single vector and inject it into the intact immune systems of mice, which closely resemble those of patients. The results were impressive.

“We saw the targeted tumors literally melt away and disappear,” said Dr. Richard Koya, an assistant professor of surgical oncology at UCLA’s David Geffen School of Medicine and first author of the study. Inserting the antigen-specific T-cell receptors sensitizes the lymphocytes to the melanoma cells. If not for these receptors, the lymphocytes would not recognize the tumor cells as foreign.

By imaging the genetically engineered T cells as they seek out and attack the cancer, the processes of the immune system unfold. Within two to three days after being injected into the bloodstreams of the mice, the cells had found and begun to fight the melanoma, although Ribas cautions that the process might take longer in people. Regardless, the murine research offers a reasonable expectation that the battlefield in melanoma patients could be imaged with PET.

If a patient’s tumor does not respond well to the administration of the genetically engineered T cells, PET scans may indicate why, documenting whether they had not successfully found the tumor, for example, or, if they did, why they malfunctioned. Monitoring the immune response also could show how the lymphocytes might be engineered to better fight tumors.

Ribas and his team are working now on creating the means for inserting T-cell receptors and reporter genes into lymphocytes for use in humans. If all goes well, clinical studies could begin in about a year, he said.

Conducting these tests will be more difficult than in the laboratory. About one million genetically engineered lymphocytes were created and injected into each mouse. Human patients will require about a billion each.