Cancer Vaccines and Immunotherapy

Background for this article can be found in and . 

Cancer vaccines are not just a dream for the future: several FDA-approved vaccines are cancer prevention vaccines. The vaccine and the (HPV) vaccines prevent infection with cancer-causing viruses. By preventing the viruses from infecting body cells, these vaccines block the process that could eventually lead to runaway cancer cell growth and damage to the body.

Viruses, however, do not cause most cancers. Researchers face the challenge to use the model of the immune response to viral infection of cells to develop vaccines for cancers not caused by viruses.

This idea is not so far fetched. Just as the immune system constantly protects the body from harmful viruses and bacteria, it also plays a vital role in protecting the body from cancer. Many cancerous cells express markers, called antigens, that act as targets for the immune system. In many cases, immune cells recognize the cancerous cells and destroy them. However, some cancerous cells can hide from the immune system or suppress it, or large numbers of cancerous cells simply overwhelm the immune system’s ability to clear the cells. The cancer cells can then divide and spread unchecked, damaging tissues and organs as they do.

Today’s researchers are devising vaccines they hope will trigger the immune system to attack cancer cells reliably and effectively. They are also exploring other ways to boost the immune system’s response to cancerous cells.

Therapeutic Vaccines

The HPV and hepatitis B vaccines are preventive vaccines. That is, they work by preventing an infection that could lead to cancer. A therapeutic cancer vaccine, on the other hand, would be used to treat cancer after it has already appeared. There are two main types of such therapeutic vaccines: autologous vaccines and allogeneic vaccines.

Autologous Cancer Vaccines

Autologous means “derived from oneself” – so an autologous vaccine is a personalized vaccine made from an individual’s own cells—either cancer cells or immune system cells.

To make an autologous cancer cell cancer vaccine, cells from a person’s tumor are removed from the body and treated in a way that makes them a target for the immune system. They are then injected into the body, where immune cells recognize them, disable them, and then do the same to other cancer cells in the body. Ideally, memory immune cells would persist in the body and respond if cancer cells returned. The goal may be to treat the cancer present in the body or to prevent tumors from recurring after more conventional cancer treatments, like surgery, radiation, or chemotherapy, have eliminated most or all of the cancer.

Several Phase 2 and Phase 3 trials of such autologous cancer cell vaccines are in process or have been completed, though none has been licensed.

Another approach to autologous cancer vaccines is to use an individual’s own immune cells to make the vaccine. The US FDA has licensed one autologous vaccine made from immune cells. Sipuleucel-t (Provenge®) is an autologous immune cell prostate cancer vaccine. It has been shown in clinical trials to extend life for men with treatment-resistant metastatic prostate cancer.

Sipuleucel-t is produced and works in the following manner:

1. Patient goes to lab to get blood drawn.
2. Lab isolates a certain type of immune cell from patient’s blood.
3. Lab technicians expose the immune cells to a prostate-cancer antigen fused with an immune-cell stimulator.
4. Treated immune cells are infused back into the patient.
5. Treated immune cells signal other immune cells to attack prostate cancer cells.

Several Phase 2 and Phase 3 trials of other autologous cancer cell vaccines are in process or have been completed. For example, researchers at the University of Pennsylvania have developed an experimental breast cancer vaccine. This vaccine uses immune cells from patients with a certain type of early breast cancer: immune cells are extracted and exposed to a tumor antigen and immune-cell stimulators, and then injected back into the body. The treated cells will then respond to cells expressing the target antigen. The strategy behind this particular vaccine is to use it in a very early stage of a certain type of breast cancer, before the body has become host to a large population of cancer cells. The vaccine showed some promise in a Phase 1 trial: most vaccinated women had fewer cells expressing the tumor antigen after vaccine treatment than similar women who did not receive the vaccine. Study on this vaccine continues.

Allogeneic Cancer Vaccines

“Allo-” means other. Allogeneic cancer vaccines are made from non-self cancer cells grown in a lab.

Several allogeneic cancer cell vaccines have been tested and are being tested, including vaccines to treat pancreatic cancer, melanoma (skin cancer), leukemia, non-small cell lung cancer, and prostate cancer. Allogeneic cancer vaccines are appealing because they are less costly to develop and produce than autologous vaccines. So far, none has been shown to be effective enough to be licensed.

Several allogeneic immune cell vaccines have been tested in early stages.[9],[10

Protein or Peptide Cancer Vaccines

The autologous and allogeneic vaccines discussed above are whole-cell vaccines: they are made from entire cancer cells or immune system cells. But some cancer vaccines in development are made from parts of cancer cells. These parts are proteins from cells, or even smaller components called peptides, which are sections of proteins. These proteins and peptides can be delivered as a vaccine alone, coupled with carriers such as viruses, or in combination with immune-stimulating molecules. As with most other therapeutic cancer vaccines, these protein or peptide vaccines for cancer are still in clinical trials.

DNA Vaccines

Another approach to therapeutic cancer vaccines uses DNA associated with tumor antigens to mount an immune response to an existing tumor. Generally, this involves vaccinating the cancer patient with a preparation containing DNA rings called plasmids. The plasmids, while not taken up into the patient's own cellular DNA, prompt body cells to produce key tumor antigens. Those antigens then signal immune cells to start responding to similar antigens on existing cancer cells in the body. Human trials of DNA vaccines to target many cancers, including breast cancer, HPV-related cancers, prostate cancer, and melanoma, are underway.

Other Approaches

Vaccines that work in the ways described above are just one tool to harness the immune system to fight cancer. Other therapies, some used for cancer treatment for many years, work to enhance different parts of the immune system to mount specific responses to cancer-related antigens.

BCG and Bladder Cancer

BCG is a tuberculosis vaccine. It is made from live but weakened bacteria related to the ones that cause tuberculosis. BCG has been used for many decades as a treatment for early stage bladder cancer. BCG in solution is introduced into the bladder and left there for several hours. The patient voids the liquid after a time. Some bacteria remain in the bladder tissue and work as an immune system stimulant. They attract large numbers of infection-fighting cells to the bladder, where those cells also target the cancer cells.

Monoclonal Antibodies

Antibodies are proteins that target antigens. They are produced in the body by immune system cells. Antibodies may mark an antigen for destruction, or they may prevent an antigen from attaching to a receptor on a body cell. Technology is increasingly being used to generate monoclonal antibodies (MAbs)– “mono” meaning they are a single type of antibody targeted at a particular antigen, and “clonal” because they are produced from a single parent cell. 

Some mABs work by attaching antigens to cancer cells and marking them for destruction by other immune system cells. Other mABs signal immune system cells to attack cancer cells. Others interrupt signals that tell cancer cells to divide. One of the most widely used mABs, trastuzumab (Herceptin®), works this way: these mABs attach to growth factors on a certain type of breast cancer cell and lead the cells to stop dividing and die.

mABs may be linked to radioactive or chemical agents—these are then called conjugated mABs. The conjugated mAB helps deliver the radioactive or chemical agent to a targeted cancer cell so that it can be destroyed.

Cytokines

Cytokines are proteins secreted by immune system cells, which play an important role in signaling to other immune system cells. For treatment of certain cancers, various cytokines are made in the lab. They are given to patients via injection into the skin or muscle, or into a vein. There are three types of cytokine therapies for cancer treatment:

• Interleukin boosts immune cell growth and division.
• Interferon can help immune system cells neutralize cancer cells and could suppress cancer cell growth.
• GMS (granulocyte-macrophage colony-stimulating factor) boosts immune cell production in the body. GMS may be used alone or given with other compounds.

Conclusion

Researchers must carefully evaluate which cancers are most suitable for a therapeutic vaccine approach. Generally, the cancers that are the best candidates are those whose treatments are associated with high costs and therapies that are less effective, or therapies that involve the risk of serious side effects for the patient. Cancers such as lung cancer, pancreatic cancer, and breast cancer are such candidates for vaccine therapy. Much study, insight, and skill will be needed to develop these vaccines.

Thanks to Caitlin E. Lentz, PharmD, and others for reviewing this article. 

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