CancerQuest | Whole Cell Vaccines

Whole cell vaccines involve the injection of tumor cells that have been weakened or killed so they cannot divide. These whole tumor cells are injected along other compounds, often protein cytokines, that will enhance the immune response. See Cytokine Therapy.

Whole cell vaccines fall under the three general categories:

Autologous vaccines
Whole cell vaccines can be prepared with tumor cells isolated from a patient to be injected into the same patient (Auto=self). The idea is that these tumor cells will have the exact same proteins (antigens) on their surface as the patient's tumors. The antigens fragments that are taken up by APCs and presented to T cells will be specific to the patient's tumor. This creates a highly tumor-specific immune response.

Allogeneic vaccines
Whole cell vaccines can also be prepared with tumor cells isolated from a different patient with the same type of cancer (Allo=other). As in autologous whole cell vaccines, the idea is that these tumor cells will have a very similar or exact pattern of antigenic proteins as the patient's tumors. The protein fragments taken up by the patient's APCs and presented to T cells will be specific to the patient's tumor. This again creates a highly tumor-specific immune response.

Gene-modified vaccines
The process of preparing whole cell vaccines involves isolating a patient's tumor cells and growing them in the laboratory. An extension of this strategy is to genetically modify the patient's tumor cells while they are in the laboratory. Genes may be inserted into the cells that cause them to have new proteins on their surface. The new proteins include immune signaling and stimulating molecules, such the cytokines interleukin-2, granulocyte-macrophage colony-stimulating factor (GM-CSF) and other stimulatory molecules. Genetically modified tumor cell vaccines create cells that express the tumor-specific antigens as well as the new immunostimulatory molecules on their cell surface. These cells can then be injected into a patient. The combination of molecules on the surface leads to an increased immune response. The added molecules on the surface of the modified tumor cells stimulate the immune system to attack the tumor cells left in the body, even though those cells do not have the new proteins on their surface.⁽¹⁾

Whole cell tumor vaccines are attractive because they are highly patient and tumor specific. The draw-back to these vaccines, however, is that it is very time consuming and expensive to create individualized vaccines for each patient. Additionally, it may be impossible to isolate and grow a patient's tumor cells in the laboratory, because some tumor cells do not live for a long time outside of the body.

Another concern is that if a vaccine were created with that increased the immune response of the patient to a protein antigen that is found on many normal cells, the vaccine would stimulate the immune cells to kill normal cells, which would obviously be bad for the patient. Nevertheless, there are many ongoing clinical trials using this strategy.