Dendritic cell vaccines have two main ingredients — frozen cells from the patient’s tumor, removed during surgery, and frozen white blood cells from the patient, removed in a process called leukapheresis.

Technician Guihua Jiang, Ph.D., mixes cells in a culture flask, one step in the vaccine production process.

Seven to eight days before the first vaccination, the patient’s white blood cells and tumor cells are delivered to the controlled environment of the Human Applications Laboratory, called the HAL, in the U-M’s General Clinical Research Center. According to Jim Mulé, director of the U-M Tumor Immunology/Immunotherapy Program, the center is a major reason for the program’s success.

“We have the advantage of getting our trials up and running with the full support of a clinical infrastrucure and a clean room production facility, which allows us to make vaccines right in the hospital,” says Mulé.

To produce the vaccine, technicians like Guihua Jiang, Ph.D., a senior research associate, first use a centrifuge to separate the different types of cells in the patient’s blood sample. Monocytes, the precursors to dendritic cells, are washed, fed a special blend of growth factors and placed in culture flasks. Then the cells grow in an incubator for six to seven days. During the incubation period, the number of cells will expand up to 30 times.
Two to three hours before the patient’s first scheduled vaccination, Jiang washes the dendritic cells and mixes them with cells from the patient’s tumor. Samples of the vaccine are removed for FDA-mandated tests for contaminants and toxins, which are performed in a separate U-M laboratory by quality control analysts. If the vaccine passes all quality control tests, Jiang fills an ordinary syringe with about one-half milliliter of the milky-white vaccine and carries it to the U-M Cancer Center where it must be injected into the patient’s thigh within 30 minutes.

Without a facility like the HAL, with technology that meets the U.S. Food and Drug Administration’s stringent standards for gene, cell and tissue-based therapies, clinical research on cancer vaccines would not be possible. Expanded and upgraded in 1995 with funding from the National Center for Research Resources and the U-M Health System, the HAL is a self-contained, HEPA-filtered clean room facility with four production modules.

The level of cleanliness in the HAL is meticulously maintained. Research associates wearing sterile white coveralls, boots and masks enter through an air lock. Staff technicians adhere to a strict cleaning protocol — regularly taking apart and sterilizing all the equipment and washing the floors, walls and ceilings. Everything inside is tested routinely to be sure that all surfaces, equipment and even the air itself are sterile.

“It’s our job to prove to the FDA that we are processing the right cells, giving them back to the right individual, and that the cells are alive and germ-free,” says Blake J. Roessler, M.D., an associate professor of internal medicine-rheumatology and director of the HAL. “We try to be as close as possible to pharmaceutical industry manufacturing production standards.”

–SFP

Also:

Harnessing the Power of the Human Immune System

The Making of a Cancer Vaccine