HEIDELBERG—A "proof of concept" study from researchers at the German Cancer Research Center shows that tumor-reactive memory T cells already present in the bone marrow of many cancer patients can be mobilized, restimulated, and deployed against the individual’s own breast, ovarian, or cervical tumor.
The research team, led by Drs. Volker Schirrmacher, Markus Feuerer, and Victor Umansky, think that cells from cancer patients’ own bone marrow might be activated by individualized tumor vaccines ex vivo and then be given back to the patient where they should attack tumor deposits through a "graft-vs-tumor" effect without reacting against normal cells.
A paper detailing the breast cancer data and published in Nature Medicine showed that breast cancer patients store tumor-reactive T cells in their bone marrow and that T cells from most patients can be reactivated into cytotoxic effector cells that will destroy the "parent" tumor xenotransplanted into NOD/SCID mice.
Similar memory cells exist in the peripheral blood but could not be reactivated into effector cells. The marrow memory cells are exquisitely specific. They responded only to lysates of tumor cells, not to preparations from normal cells.
Professor Schirrmacher told ONI that a single dose containing 5,000,000 × 10³ T cells and 1,000,000 × 10³ autologous dendritic cells was enough to produce "a strong, long-lasting graft-vs-tumor reactivity" and reduce the tumor to only its stromal scaffolding.
Tumor regression was associated with infiltration by human T cells, apoptosis of tumor cells, and tumor necrosis. Dr. Schirrmacher is head of the Cellular Immunology Laboratory at the German Cancer Research Center, Heidelberg.
"Based on experimental studies in animals, we had predicted in 1994 that the bone marrow might be a special compartment for immunological memory and tumor dormancy," Dr. Schirrmacher said. "We decided to test this in humans and investigate bone marrow from cancer patients, but we did not expect the results to provide so much support for our original idea."
