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Healthy individuals typically survive the common cold and many more serious maladies because the immune system is generally highly efficient at targeting and destroying foreign cells. But, in the case of cancer, the immune system's penchant for not attacking the body's own cells works against us -- the immune system does not typically attack cancer cells because the body has produced them (and because they carry the chemical signatures to prove it).
Yet, investigators at the Abramson Family Cancer Research Institute have shown in animals that it is possible to induce the immune system to attack normal tissues. These findings suggest that it may be possible to induce the immune system to attack cancer cells even though they are the product of one's own cellular machinery.
One approach to enhancing the ability of the natural immune system to recognize and eliminate tumor cells involves removing some of a patient's immune cells found in the blood (e.g. T cells) and stimulating them to proliferate so they can attact the cancer effectively.
Cell Infusion Therapy
Click on each step for further information.
| 1. |
Obtain cells from patient and enrich or isolate particular cells of interest
Patients enrolling in clinical trials at the Abramson Cancer Center at the University of Pennsylvania undergo apheresis at the Hospital of the University of Pennsylvania (HUP) Blood Bank. Apheresis is a procedure by which the white blood cells are removed from the blood and red cells and other components are returned to the patient. The procedure usually takes about 3 hours and is a common procedure performed in blood banks. The apheresis product can then be transported to the HUP blood bank cell processing laboratory for cryopreservation in liquid nitrogen. Fresh cells or cryopreserved cells then proceed to the CCPF. For clinical trials conducted in collaboration with other medical centers, the apheresis and initial processing may be performed at the remote medical center's blood bank.
Particular populations of cells can be enriched or isolated in the CCPF. This is done to maximize the purity of a therapeutic population of cells. Depending on the relative percentage of the cell population of interest, the unselected cells can be negatively enriched (unwanted cells removed) or positively selected (desired cells isolated). Monoclonal antibodies directed against particular cell surface markers and microscopic magnetic beads aid in this procedure. |
| 2. |
Stimulate cells to grow
White blood cells can be stimulated to grow in the laboratory by a variety of methods. The cells are cultured in a nutrient broth termed media, but need a form of stimulation in order to divide and grow. This is provided by monoclonal antibodies directed against cell surface receptors. The monoclonal antibodies are added to the cells on microscopic magnetic beads. The whole mixture of cells, growth media and monoclonal antibodies immobilized on beads is added to a gas permeable plastic bag and the cells are placed in a humidified 37o Celsius incubator. The cells begin to divide and after a few days, clumps of cells can be seen growing in the bags. |
| 3. |
Insert potentially therapeutic genes into cells
Immune cells and stem cells can be redirected , given anti-tumor or anti-viral properties or given enhanced survival properties via the transfer of therapeutic genes. These genes are inserted first into a carrier to serve as a delivery vehicle to the cell termed a vector. The vector, added to an activated cell population, enters the cell and releases its payload, the gene. The cell then takes up the gene and expresses the product. |
| 4. |
Large scale cell expansion
Standard cell culture flasks pose problems for large scale culture of patient cells. Firstly, only a few tens of millions of cells can be grown in one flask. To reach therapeutic numbers of cells, dozens of flasks need to be used, which is very labor intensive. Secondly and more importantly, these flasks must be opened to add media or sample cells during culture. Although this is done in a cabinet with filtered air, the potential for contamination of the culture with bacteria, mold or fungus remains. For these reasons, the CCPF culture cells in closed gas permeable plastic bags. Tubing leads on the bags and a variety of connecting devices allow the cells to be grown in a closed system with minimal risk of contamination. In addition, these bags can contain several billion cells each and thus reduce the "hands-on" time needed to maintain the culture. |
| 5. |
Remove beads and wash cells
As mentioned above, cells are stimulated via monoclonal antibodies linked to microscopic magnetic beads. These beads must be removed prior to reinfusing the cells to the patient. To do this, the cell culture is passed over very powerful flat magnets. The beads are retained on the magnets and the cells flow through. The next step prior to infusion is to wash the cells out of the nutrient media and into an infusible solution. At times, the volume of the cell culture can be as much as 10 liters (2.5 gallons) or more. This is obviously too much volume to infuse and the cells need to be concentrated as well. Washing and concentration is performed in a specialized centrifuge. This centrifuge contains a disposable belt and tubing that can be linked to the cell culture bags, maintaining a closed system. After washing the cells and resuspension in infusion solution, the cells are ready to be transported to the clinic if all quality control and release criteria have been met. |
| 6. |
Quality control
Prior to reinfusion, the cells must be certified to be free of contaminating agents and to meet certain requirement for cell function, viability and phenotype. This is the responsibility of the Quality Control component of the CCPF. Testing of contaminating agents such as bacteria, fungus, mycoplasma, bacterial endotoxin, and HIV p24 (if applicable) are performed in our laboratory or on contract with clinical reference laboratories. Cell viability and phenotype are performed in our laboratory. The results from these assays are recorded on forms prior to the release of cells from the CCPF and accompany the cells to the reinfusion site. An independent Quality Assurance officer oversees the Quality Control process. |
Alternatively, one might stimulate a similar immune system response by injecting patients with a vaccine based on the particular cancer.
Translational Research currently has under way clinical trials employing each of these methods.
Related Links
National Cancer Institute -- Biological Therapies: Using the Immune System To Treat Cancer
National Cancer Institute -- Treating Cancer with Vaccine Therapy |
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