Vaccines are designed to stimulate the immune system to mount an immune response against the target in the vaccine. For instance, the flu vaccine contains pieces of the flu virus, and stimulates the immune system to make cells that fight the flu virus. The flu vaccine needs to be given at least two weeks before exposure to the flu. This is an example of a preventive vaccine. The flu vaccine can stimulate long-lasting immunity to the strain of flu used in the vaccine.
Cancer vaccines are different in that they are not preventive. Rather, cancer vaccines are therapeutic-they are used to treat the disease rather than prevent it. Like the flu vaccine, cancer vaccines are designed to stimulate the immune system to mount a response toward the target-in this case the cancer cells. Unlike flu virus which is foreign to the body, cancer cells are not foreign and generally do not stimulate a strong immune response on their own. So cancer vaccines use other substances or cells to help the immune response along.
Some of the substances in cancer vaccines are called cytokines, which act as “immune hormones.” Other substances are called heat shock proteins. Heat shock proteins and cytokines can help alert the immune system to the information about the cancer cells. This alert helps certain immune cells that are sensitive to the cancer cells to divide. This new “army” of cells will kill any cancer cell they come in contact with.
The cells that are most efficient at stimulating an immune response are called dendritic cells. Dendritic cells are a specialized immune cells found throughout the body. To make a vaccine, precursor cells are taken from a blood sample of the patient and grown in the laboratory. Information about the surface of the patient’s cancer cells is placed inside dendritic cells that are grown in the laboratory. When the cells are injected they can activate an immune response toward the cancer cells. As with cytokine and heat shock protein activation, the alerted cells divide and kill cancer cells they come in contact with.
Unlike chemotherapy cancer vaccines generally have few side effects. Here at the clinic we use all the types of cancer vaccines described above. The results achieved vary with tumor, type of tumor and stage of disease.
Cancer vaccines represent an innovative potential cancer therapy — a therapy that seeks to harness the body’s own defenses to fight the uncontrolled growth and spread of cancer cells.
The immune system has the ability to recognize the difference between “self” and “non self,” that which is and is not a naturally occurring molecule in the body. In the case of cancer, the difference between cancer cells and normal healthy cells is sometimes so slight that they go unnoticed by the immune system and no response occurs, or the immune system is overwhelmed. The body is “tolerant” of the cells allowing them to multiply in the body. Cancer vaccines seek to “break” this tolerance.
Cancer vaccines are designed to introduce molecules expressed on cancer cells into the body in a new way that awakens the immune system to respond and destroy the cancer cell. These vaccines attract immune cells such as dendritic cells that engulf the vaccine cells which include “antigens” or proteins on their cell surfaces, and then present (exhibit) fragments of these antigens. These immune cells, known as “antigen presenting cells” (APCs), then signal other immune cells to mature and attack the specific invading antigen. Lymphocytes, including helper T cells, killer T cells, and B cells, are called into action. Helper T cells release cytokines, chemical messages that recruit other immune cells, and killer T cells engulf the antigen (and the cell it is attached to) the APCs presented to it. In addition to awakening the cellular side of the immune system to the tumor cell, some cancer vaccines stimulate the humoral side of the immune system, which includes antibodies, into action as well.
Types of Cancer Vaccines
Research and development efforts are currently under way to develop therapeutic cancer vaccines for the treatment of multiple forms of cancers. Currently, there are two primary approaches being explored in the development of making cancer vaccines—the “antigen-specific” approach, and the “whole cell” approach.
The antigen-specific approach seeks to make a vaccine that stimulates an immune response to a specific antigen or antigens that are believed to be unique to a specific type of tumor. This approach may result in a highly specific antitumor response, however poses the challenge of successfully identifying the specific antigens that are most highly expressed on a given tumor. Failure to identify the appropriate antigens could result in lower or no efficacy.
One approach to developing an antigen-specific vaccine involves the removal and isolation of a patient’s dendritic cells, one type of APC. The dendritic cells are exposed to antigens that are believed to be associated with a specific tumor type, and are given time to ingest, process, and “present” the antigens. The cells are then reintroduced into the patient in vaccine form.
Whole Cell Approach
The whole cell approach uses whole cancer cells to make the vaccine, not just a specific antigen. Since whole cells express multiple—sometimes thousands of—antigens, there is potentially a greater chance of stimulating an immune response since this approach does not require choosing specific antigens which may or may not turn out to be appropriate for the patient. Cell Genesys is pursuing a whole cell vaccine approach with its GVAX® cancer vaccines.
Whole cell vaccines can be either patient-specific (made completely from the individual’s own tumor cells), non patient-specific (made from a “cell line”—tumor cells that are grown in a laboratory), or a mixture of the two. Patient-specific vaccines may offer some advantages over non patient-specific vaccines when treating cancers that involve many different cell types with few like characteristics (e.g. non small-cell lung cancer). Using the patient’s own tumor cells may increase the likelihood of creating an individualized vaccine that effectively stimulates an immune response against all cell types associated with specific form of cancer being treated.
While some cancer vaccines are designed to stimulate an immune response based solely on the presence of antigens, others are being developed that utilize antigens as well as cytokines to mount an attack against cancer cells. Cytokines are chemical messages that stimulate other immune cells to attack antigens. Some researchers are exploring the idea of creating vaccines comprised of cells that have been genetically modified to secrete a cytokine such as GM-CSF, interleukins, and interferons. The presence of these cytokines may potentially help “jump start” the immune system to launch a more robust and efficacious immune response.
Possible Benefits of Cancer Vaccines
In addition to providing a new treatment option for patients who have failed other therapies, clinical data suggest that cancer vaccines may offer therapeutic advantages over existing therapies:
1. Favorable Side Effect Profile: Unlike many traditional cancer treatments such as chemotherapy and radiation therapy, cancer vaccines have generally been associated with very few side effects. This favorable side effect profile may potentially enable patients to maintain a higher quality of life during the course of treatment.
2. Combination Therapy: Numerous clinical trials are being conducted evaluating the use of cancer vaccines in combination with other traditional therapies such as chemotherapy, radiation therapy, and stem cell transplantation. Combination therapies offer the potential of improving/enhancing the efficacy of these traditional treatments.
The Current State of Cancer Vaccines
Research and development efforts are currently under way at numerous organizations to thoroughly evaluate the safety and efficacy of different approaches to cancer vaccines. Currently, cancer vaccines are being evaluated in multiple human clinical trials for many types of cancer and are available only in the clinical trial setting.