IMMUNE RESPONSE TO CANCER OBSERVED

The UCLA study is expected to lead to new ways to test immune-based therapies for cancer and other immune system-related diseases and to monitor human response to cancer treatments much more quickly and without the need for invasive biopsies, said Dr. Owen Witte, a Jonsson Cancer Center researcher, a professor of microbiology, immunology and molecular genetics and the study's senior author.

The study appears in the Nov. 29, 2005 issue of the Proceedings of the National Academy of Sciences and will be published in an early online edition this week. "This study is teaching us about how the immune system recognizes cancer. That's something we couldn't see before," said Witte, who also serves as director of the UCLA Institute for Stem Cell Biology and Medicine and is a Howard Hughes Medical Institute investigator. "We were able to watch the primary immune response, the very first reaction of the immune system to the presence of cancer in body. This gives us a new tool that will allow us to evaluate novel ways to help the immune system become better at finding and eliminating cancer as well as studying autoimmune and immune deficiency disorders."

In the study, Witte and his team removed bone marrow from a laboratory animal and marked all the cells that would be derived from the bone marrow stem cells with two radioactive probes that are detected by a PET scan. Because they used different probes that show in different ways the cell functions, the research team was able to see more of what was going on in the immune system as it fought cancer, Witte said. The bone marrow was then put into a different laboratory animal and cancer was introduced so researchers could monitor the immune response, the movement and behavior of lymphocytes, and myeloid cells--the cells the immune system uses to fight foreign invaders. "We were able to observe the moment that the immune system sees the foreign antigens of the cancer in the body and its response, which starts in the local draining lymph nodes," Witte said. "We saw an increased number of lymphocytes and myeloid cells in those lymph nodes, then saw them migrating to the tumor in an attempt to kill the cancer."

One of the probes used to mark the immune system cells and cause them to light up under PET scan, the agent FDG, already is approved for use in humans, Witte said. This could prove valuable in monitoring human response to immune-based therapies such as cancer vaccines. Researchers could use FDG and PET scanning, for example, on a patient receiving an experimental cancer vaccine. Researchers could determine much more quickly whether the therapy was working by monitoring immune response in real time. "We could see much sooner if the therapy was effective, without the need for a biopsy," Witte said. "We would also know very rapidly, within a week or two. Prior to this, we had to wait many months to find out if a therapy was working."

Jonsson Cancer Center researchers testing a melanoma vaccine will be collaborating with Witte and his team to monitor immune response in those study volunteers, Witte said. If the therapy is not working, the volunteers would not have to undergo months of unsuccessful treatment and could potentially find another therapy to try.

PET scanning, developed by UCLA scientist Michael Phelps, is a highly sensitive detection method that provides three-dimensional information within the body. The probes used in this study are labeled with positron-emitting radioisotopes, which allow researchers to measure the rates of biochemical processes in the tissue, processes such as immune response. "Many of the problems in evaluating immunotherapy protocols stem from the lack of effective tools to follow the extent and duration of responses to treatment," the study states. "In this study, we have demonstrated a strategy to monitor a specific primary immune response against a tumor challenge."