|The Making of a Cancer Vaccine
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
“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
Harnessing the Power of the Human Immune
The Making of a Cancer Vaccine