Fusion Cell Vaccine Kills Multiple Myeloma Cells in Vitro

NEW ORLEANS—Multiple myeloma cells can be fused to dendritic cells and the resulting fusion cells used to selectively kill myeloma tumor cells in vitro, according to a poster presentation at the 41st annual meeting of the American Society of Hematology (ASH).

“We are trying to generate a vaccine for the treatment of minimum residual disease in multiple myeloma in the post-transplant setting,” the report’s lead author Noopur Raje, MD, said in an interview with ONI. Dr. Raje is an instructor in medicine at Harvard Medical School.

“The approach we are using is to fuse the whole tumor cell to an autologous dendritic cell with the hope of being able to present both known and unknown antigens to the host,” rather than presenting just a single antigen, as many dendritic-cell-based vaccines do, Dr. Raje explained.

In the study, cells from two human multiple myeloma cell lines (HS Sultan and SKO-007) were fused to dendritic cells from normal donors, which were cultured in the presence of GM-CSF and interleukin-4.

The researchers then tested the ability of these fused cells, multiple myeloma cells alone, and dendritic cells alone in vitro to prime naïve cytolytic T cells to act against multiple myeloma cells.

After three weekly stimulations, the cytolytic T cells primed with fused cells had killed 35% to 45% of the tumor cells. In contrast, T cells treated with just myeloma cells or just dendritic cells did not cause cell lysis in tumor cells.

“We’ve gone on to do patient samples,” Dr. Raje added, “and we’ve seen that the patients’ own T cells actually respond to this kind of approach.”

In autologous mixed lymphocyte reactions using T cells derived from patients, fused cells (but not myeloma cells alone or dendritic cells alone) caused autologous T cells to proliferate. Dr. Raje said he hopes to begin a phase I clinical study early this year.