Cancer is a leading cause of death in the industrialized world, second only to cardiovascular diseases. It is estimated that the number of people living with cancer is increasing. The most common malignancy diagnosed in women is breast cancer.
The objective of cancer immunotherapy is to enhance the patient’s immune system, especially T cells, to fight cancer. In recent years cancer immunotherapy has emerged as a promising cancer treatment.
Breast cancer survival rates are increasing in the United States. This trend is partly attributed to improvement in therapeutic strategies. Cancer immunotherapy encompasses various strategies to harness a patient’s own immune system to attack and kill tumor cells specifically.
A living drug
Clinicians and researchers have long hoped that the patients’ own immune systems can be employed to eradicate cancer. Unlike other treatment strategies, cell-based immunotherapy is like a living drug that can adapt to stay ahead of evolving tumor cells.
Cell-based immunotherapy also has the benefit of remaining effective even when conventional cytotoxic or targeted drug therapy fails. In addition to the direct attack on tumor cells, the immune system may prompt indirect effects by attacking the tumor. By “resetting” the immune system to an anti-tumor surveillance status, it protects against tumor outgrowth.
Several immunotherapies show promise in the treatment of aggressive breast cancer. Here are three of these immunotherapies.
Breast Cancer Vaccines
The fundamental concept behind vaccination is exposure to a specific antigen. Through active immunity, the immune system develops memory and can recognize and swiftly respond to the antigen during future exposures.
Vaccination, commonly used in the prevention of infectious diseases, has been applied to the development of vaccines to prevent and treat cancer.
Preventive vaccines can target a virus known to be important in the malignant transformation of human cells (e.g., human papillomavirus and cervical cancer) or antigens expressed early in the process of tumorigenesis. Therapeutic vaccines typically target known cancer antigens. Intramuscular delivery of peptide (synthetically produced) antigens is the most basic technique of antigen exposure.
While peptide vaccines are customizable, easy, and relatively inexpensive to produce, injected peptides are readily degraded and have variable ability to provoke an immune response. Despite eliciting a measurable immune response, the impact on tumor growth has not always been substantial. In this case, combination therapies and alternative methods of antigen delivery can be added to the treatment.
Immune Checkpoint Inhibitors in Breast Cancer
A checkpoint is a stage in the cell division cycle where the cell elects to go ahead with division. This checkpoint prevents a cell from dividing when it shouldn’t. For example, if the cell’s DNA is damaged or there isn’t any room for more cells in an organ or tissue.
Immune checkpoints are key regulators of the immune system that, if stimulated, may inhibit the immune response to a stimulus, such as cell-based immunotherapy. Some cancers will protect themselves from attack by stimulating immune checkpoint targets.
Checkpoint Blockade – Immune checkpoint Inhibitors can block inhibitory checkpoints, restoring the immune system function. Immune checkpoint inhibitors can produce durable tumor remission and induce long-standing anti-tumor immunity in a subgroup of breast cancer patients.
Immune checkpoint inhibition has emerged as an effective treatment for various malignancies, with FDA approvals for new indications occurring rapidly. The study of immunotherapy in breast cancer has been relatively delayed compared to other malignancies. Until recently, breast cancer was not thought to be a disease that provoked an immune response.
We now know that many breast cancers are immunogenic and are enriched in tumor-infiltrating lymphocytes (TILs). Reactivating the immune system to eradicate breast cancers has emerged as a promising treatment strategy, and immune checkpoint inhibition has demonstrated activity in both advanced and early-stage breast cancer.
Oncolytic Viruses
An oncolytic virus is a virus that preferentially infects and kills cancer cells. The development of oncolytic viruses as cancer therapies is a product of two disciplines, virology and immunology, and identifying tumor-associated antigens.
Viruses can be engineered to preferentially enter tumor cells by altering their target receptor to a known cell surface antigen or capitalizing on defective signaling proteins in tumor cells.
Alterations in viral nucleic acid and protein metabolism can be employed to harness the naturally higher expression of key enzymes in proliferating tumor cells compared to normal cells. Once administered to the patient, viruses infect tumor cells, which are killed by intracellular replication of the virus. Also, by dealing out viral antigens onto MHC-I cell surface recognition elements, virus-specific T cell clones are activated to destroy tumor cells.
Breaking down the cell membrane with an oncolytic virus is much like a whole tumor cell vaccine. The breakdown of the cell contributes to the overall anti-tumor immune response by releasing tumor-associated antigens. These are then processed by antigen-presenting cells – a phenomenon known as epitope spreading.
Adoptive Chimeric Antigen Receptor T cell (CAR T) Therapy
Chimeric antigen receptor T-cell (CAR-T) is a T-cell that has a component that directly binds the target antigen and transmits an activating signal into the CAR-T cells, triggering its action against the target cell-activated on the surface of the T-cells, every T-cell converts into an antigen-specific killer T-cell. CAR T-cells are made by genetically engineering an antigen-binding cell surface (scFv) into a T cell toxic to cancer cells.
The chimeric antigen receptor T-cell is a “bispecific antibody.” Bispecific antibodies recognize both the target antigen and the activating receptor on the surface of an immune effector cell. This dual-action offers an opportunity to redirect immune effector cells to kill cancer cells.
Advances in antibody genetic engineering and antigen profiling of malignant cells have led to many bispecific antibodies. There have been significant advances in designing and applying bispecific antibodies for intravenous and local injection in the past 25 years.
Conclusion
Different anticancer immunotherapy treatments have the potential to cure and end all forms of cancer eventually. Great promise and hope are now emerging from a remarkable amount of data accumulated in this field in a very short time. To learn more about the immune system, how it works, and how immunotherapy can take advantage of its mechanisms, read – A Fascinating Behind The Scenes Look At Your Immune System.