For many years, the treatment of cancer was focused primarily on surgery, chemotherapy, and radiation. However, as researchers learn more about how the body fights cancer on its own, therapies are being developed that harness the potential of the body's defense system in this fight, including efforts to prevent some forms of cancer.
The body's defense system - called the immune system - consists of a network of specialized cells and tissues that fight infection and disease. Therapies that use the immune system to fight or prevent cancer are called biological therapies.
Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are ‘tolerated’ by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules.
Unlike the vaccine you might receive for the flu, most cancer vaccines aren't intended to prevent you from getting cancer. Rather, the majority of cancer vaccines being studied aim to condition your body to recognize cancer cells as invaders. Vaccines may be used to attack cancer cells in several different ways. In one method, the vaccine consists of cancer cells that are inactivated, usually through radiation, and injected into your body. These cancer cells can't grow and form new cancer, but they still carry the signals that activate your immune system to attack cancer in your body. Some vaccines are made of cells from your own cancer. Still others are made of cells from your immune system (dendritic cells). Scientists manipulate these cells to recognize cancer cells and then inject the manipulated cells into your body. Once in your body, the manipulated cells target the cancer cells, as well as recruit other cells in your immune system to join the fight.
What is a vaccine?
A vaccine is a substance designed to stimulate the immune system to launch an immune response. This response is directed against specific targets, or antigens, that are part of the vaccine. An antigen is any substance that the immune system recognizes as foreign.
Vaccines can be made using specific types of molecules from viruses or cells, including molecules from bacterial cells or human cells. These molecules may contain a single antigen or several different antigens. Carbohydrates (sugars), proteins, and peptides (pieces of proteins) are among the types of molecules that have been used to make vaccines. Molecules of DNA or RNA that contain genetic instructions for one or more antigens can also be used as vaccines.
In addition, whole viruses or cells, or parts of viruses or cells that contain different types of molecules, can be used to make vaccines. The flu vaccine, for example, is made using inactive whole flu viruses. If whole human cells are used as vaccines, they are usually treated with enough radiation to keep them from dividing (growing and multiplying) or enough to kill them.
It has been more than 100 years since the first reported attempts to activate a patient's immune system to eradicate developing cancers. Although a few of the subsequent vaccine studies demonstrated clinically significant treatment effects, active immunotherapy has not yet become an established cancer treatment modality. Two recent advances have allowed the design of more specific cancer vaccine approaches: improved molecular biology techniques and a greater understanding of the mechanisms involved in the activation of T cells.
These advances have resulted in improved systemic antitumor immune responses in animal models. Because most tumor antigens recognized by T cells are still not known, the tumor cell itself is the best source of immunizing antigens.
For this reason, most vaccine approaches currently being tested in the clinics use whole cancer cells that have been genetically modified to express genes that are now known to be critical mediators of immune system activation. In the future, the molecular definition of tumor-specific antigens that are recognized by activated T cells will allow the development of targeted antigen-specific vaccines for the treatment of patients with cancer.
CLASSIFICATION OF CANCER VACCINES
Cancer vaccines can be broadly classified into two categories: those that target shared antigens and those that target unique antigens.
Shared-antigen cancer vaccines
Shared antigens are antigens that exist in normal tissues but are overexpressed in cancer cells. Because they are expressed in normal tissues, there is an increased tolerance for them, making shared antigens less likely to stimulate immune response. Moreover, if a cancer vaccine does overcome tolerance, autoimmunity can often be an unwelcome side effect.
The majority of therapeutic cancer vaccines in development use a shared-antigen approach and differ only in the particular antigens used or the method used to attempt to overcome tolerance. Clinical testing of shared antigens to date has been largely confined to a small number of cancers, and the number of shared antigens necessary to target every cancer cell in any one patient and achieve clinical benefit across diverse patient populations is unknown.
Unique-antigen cancer vaccines
Unique antigens are antigens that occur only in cancer cells and do not exist in normal tissues. They arise from mutations that occur as the tumor cells grow uncontrollably. The vast majority of unique antigens are not only specific to cancer cells but also specific to each individual patient. As a result, the unique-antigen approach is potentially applicable to all cancer types, from solid tumors to hematological malignancies.
Currently, the only way to produce a cancer vaccine using these unique antigens is by employing an autologous approach — meaning that the antigens are derived from the same individual they are used to treat. Preliminary indications of clinical benefit associated with autologous vaccine treatment have been observed in every indication tested — close to a dozen types of cancer. Autologous cancer vaccines in development include those utilizing whole cells, tumor lysates, RNA or heat shock proteins.
Early attempts at autologous cancer vaccines involved whole cell preparations or lysates of a patient’s tumor, which were shown to be unsuccessful, as unpurified cellular contents send both stimulatory and suppressive immune signals.
Although some success has been achieved using newer approaches, the complexity of the manufacturing process, issues with sterility, and difficulty in characterization of these complex autologous products make them less attractive from a commercial and regulatory standpoint.
Heat shock proteins
Antigenics’ approach to cancer vaccines is based on heat shock proteins (HSPs), a ubiquitous family of proteins believed to play a role in the presentation of antigens on the cell surface to help the immune system recognize diseased cells. Among cancer vaccine approaches — autologous or otherwise — the HSP approach has achieved the highest degree of independent validation by researchers worldwide, and has shown indications of clinical benefit in seven cancer types to date.