Gene, immune therapy help cancer war

Stanford University researcher Irving Weissman explains how the drug Rituxan, generically called rituximab, improves the cancer-killing effect of a new antibody that renders cancer cells vulnerable to immune attack. He spoke Monday, April 7, at the American Association for Cancer Research meeting in San Diego.

The war on cancer is getting some potent reinforcements, including a potentially broad-spectrum new weapon and genetically engineered immune cells with improved cancer-fighting abilities, speakers said at a major cancer research conference held this week in San Diego.

The American Association for Cancer Research, attended by an estimated 18,000 participants, is being held at the San Diego Convention Center through Wednesday. While it is covering the gamut of research, cancer immunotherapy is a major focus. The field began more than 100 years ago, and has lately scored impressive advances by using gene therapy to its tool kit.

The weapon is an antibody that makes a wide range of cancer cells vulnerable to immune attack. It's close to entering human clinical trials, said Irving L. Weissman, a Stanford University professor leading that project. The antibody neutralizes a chemical signal many cancers exude to decoy the immune system, Weissman said in a Monday morning plenary session.

The antibody is being tested first in acute myeloid leukemia patients, backed by $20 million from the California Institute for Regenerative Medicine, Weissman said. The institute is interested because the target cells are cancer stem cells, the cells that proliferate to spread cancer.

Moreover, research indicates the method can be used against many solid tumors that emit the signal, a protein called CD47. These include breast, ovarian, bladder, pancreatic and colon cancer.

"Every human cancer that we've seen has CD47," Weissman said.

Animal studies show that anti-CD47 antibodies inhibit growth of transplanted patient tumors, he said. And when used against non-Hodgkin's lymphoma along with an existing antibody drug called Rituxan, the result is a potent cancer-killing effect. Immune cells called macrophages actually engulf and destroy the cancer cells.

The CD47 molecule is normally present on young cells, serving as a "don't eat me" signal to immune system cells that might otherwise attack them, Weissman said. Cancer cells have chanced on mutations that cause the protein to be made in exceptionally high amounts. So even when they might be abnormal enough to merit immune system attack, they escape surveillance.

Another approach already in the clinic is to genetically engineer immune cells called T cells to be better at fighting cancer. Carl June, a University of Pennsylvania researcher behind one of the studies, said results continue to be encouraging. This approach targets another protein abnormally made by cancer cells, CD19. Novartis is testing the therapy.

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Gene, immune therapy help cancer war