July 2, 1999 Cancer scientists at the Johns Hopkins Oncology Center have figured out a way to keep the body's cancer-fighting immune cells awake and responsive to tumor cells far longer than they normally do.
Scientists have long known that it is possible to activate immune cells to recognize molecules found on tumor cells. Over time, the ability of the immune system to respond to cancer cells diminishes. In the current research, published in the July 1, 1999 issue of Nature Medicine, the Hopkins team, working with genetically engineered mice, used an antibody to a molecule found on the surface of so-called antigen presenting cells (or APCs) to restore the ability of the immune system to respond.
"We believe APCs are key to teaching specialized immune system cells called T-cells to identify and track down cancer cells. Our strategy seeks to activate the APCs so they are better at 'priming' T-cells," says Hyam Levitsky, M.D., associate professor of oncology at Johns Hopkins and senior author. "One reason that immunotherapy of cancer frequently doesn't work is that it's very hard to keep the immune system responsive to tumors as they grow," explains Levitsky.
Researchers suspect that APC cells capture immune-triggering proteins from dying cells, including tumor cells. APCs, which are derived from bone marrow, are the only cells that are able to "present" these proteins, known as antigens, to T-cells which trigger a cascade of events that destroys cancer. "Activation of the APC has been the critical missing link in this cascade," says lead author, Eduardo Sotomayor, M.D., a fellow of the Lymphoma Research Foundation of America.
"Our method of activation, which targets CD-40 proteins on the APC, may now be used to provide a stimulant that enhances cancer vaccines used in treatment and, at the very least, prevent the immune system from becoming tolerant to cancer cells," says Sotomayor.
The T-cells studied in the Hopkins research, called CD-4+T-cells, are well known to immunologists as the same cells targeted by HIV, the virus that causes AIDS. "The CD-4+T-cell is like an army general that gives the order to killer cells to seek out and destroy foreign invaders in the body. In cancer, the immune system remains asleep, because the CD-4+T-cell never sends the order to attack. We believe the APCs can wake it up," explains Levitsky.
In addition to Levitsky and Sotomayor, other research participants including Ivan Borrello, M.D., Erev Tubb, Frederique-Marie Rattis, Ph.D., Harold Bien, Zhengbin Lu, Steve Fein, M.D., and Stephen Schoenberger, Ph.D., of La Jolla Institute for Allergy and Immunology.
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