Gene therapy for cancer is a shift in treatment from broad-spectrum approaches to more targeted interventions. Instead of external chemicals or radiation, this strategy alters or adds genes to correct a malfunction, enhance a function, or introduce a new capability to cells. The goal is to modify the genetic instructions within cells to help them recognize and destroy cancerous growths or stop them from proliferating.
This approach is designed to be highly specific, affecting cancer cells directly or stimulating the patient’s immune system to target the cancer. This precision aims to leave healthy tissues unharmed, a common challenge with conventional treatments. The field has advanced from a theoretical concept to a clinical reality, offering new options for various types of cancer.
Mechanisms of Gene Therapy in Oncology
One mechanism is CAR T-cell therapy, a form of immunotherapy that modifies a patient’s own immune cells. The process involves extracting T-cells, a type of white blood cell, from the patient. These cells are then genetically engineered in a lab to produce surface structures called Chimeric Antigen Receptors (CARs). These receptors are designed to recognize and bind to a specific protein, or antigen, on the surface of the patient’s cancer cells.
Once equipped with these new receptors, the T-cells are multiplied into the millions and infused back into the patient. The engineered CAR T-cells can now circulate throughout the body, identify cancer cells by locking onto their specific antigen, and launch a targeted attack. This method trains the immune system to see and eliminate cancer that it previously could not.
Another approach uses oncolytic viruses, which are altered to selectively target and kill cancer cells. These viruses are engineered to recognize features of cancer cells, allowing them to infect and replicate within them while largely ignoring healthy cells. The virus’s replication causes the cancer cell to burst and die, releasing new viral particles to infect nearby cancer cells. This destruction also releases tumor-specific antigens, which helps the body’s natural immune defenses identify and attack any remaining cancer.
Therapeutic cancer vaccines are a different strategy designed to treat existing cancer. Unlike traditional vaccines, these are administered to individuals already diagnosed with cancer to stimulate their immune system against tumor cells. These vaccines work by introducing cancer-specific antigens into the body, teaching T-cells and other immune components to recognize and destroy cancer cells that display those same antigens.
Cancers Treated with Gene Therapy
The application of CAR T-cell therapy is most established in treating certain blood cancers. Regulatory bodies have approved its use for specific types of B-cell acute lymphoblastic leukemia (ALL) and several types of non-Hodgkin lymphoma. More recently, its scope has expanded to include multiple myeloma, a cancer of plasma cells. Success in these areas has spurred research to adapt this technology for other blood cancers.
Oncolytic virus therapy is used in treating certain types of solid tumors, most prominently melanoma. An FDA-approved oncolytic virus therapy can be injected directly into melanoma tumors that cannot be surgically removed. This approach is also being investigated for other solid tumors, with clinical trials exploring its use in cancers such as glioblastoma and liver cancer, where direct injection is feasible.
Therapeutic cancer vaccines are being developed for a range of cancers. One vaccine has been approved for advanced prostate cancer that no longer responds to hormone therapy. This vaccine is customized for each patient using their own immune cells, which are exposed to a protein found on prostate cancer cells. Other therapeutic vaccines are in development for cancers including pancreatic and lung cancer.
Potential Risks and Side Effects
A risk associated with CAR T-cell therapy is Cytokine Release Syndrome (CRS). This occurs when the re-engineered T-cells attack cancer cells, leading to a massive release of inflammatory molecules called cytokines. This can cause high fevers, chills, and a sharp drop in blood pressure. While CRS indicates the therapy is working, it can be dangerous if unmanaged, ranging from mild symptoms to life-threatening inflammation. Medical teams are trained to monitor for CRS and administer medications to dampen this immune response.
Neurotoxicity, which involves adverse effects on the nervous system, is another complication of CAR T-cell therapy. Patients may experience confusion, difficulty speaking, or, in severe cases, seizures. The cause is believed to be related to the inflammatory environment created by the active CAR T-cells. These symptoms are typically temporary and reversible but require careful monitoring.
A more general risk is the potential for on-target, off-tumor effects. This happens when the therapy attacks healthy cells because they express the same target antigen as the cancer cells. For example, if a CAR T-cell therapy targets an antigen on lymphoma cells that is also on normal B-cells, the therapy will destroy the healthy B-cells, increasing infection risk.
Viral vectors, used in therapies like oncolytic viruses, also have risks. There is a concern that the modified virus could cause an unintended infection, particularly in a patient with a weakened immune system. Another risk involves the virus inserting its genetic material into the wrong location in the host cell’s DNA, which could disrupt a normal gene.
The Development and Accessibility of Gene Therapies
Several gene therapies have been approved by regulatory agencies like the U.S. Food and Drug Administration (FDA). Multiple CAR T-cell therapies are now confirmed as viable clinical options for various blood cancers. For certain patients with specific types of leukemia, lymphoma, and multiple myeloma who have not responded to other treatments, gene therapy is a standard-of-care option.
The landscape of gene therapy is expanding through clinical trials. Researchers are actively testing new therapies for a broader array of cancers, with a focus on solid tumors like breast, lung, and colon cancer. These have been more difficult to treat with cellular therapies due to the complex tumor environment. These trials evaluate new targets, genetic modifications, and combination approaches.
Despite scientific progress, hurdles to widespread accessibility remain. A substantial challenge is the high cost, as creating a personalized therapy like CAR T-cells is a complex and expensive process. These therapies also require specialized infrastructure, meaning they are offered at a limited number of major medical centers, restricting access for many patients.
Future research is aimed at overcoming these limitations. Scientists are working to develop new manufacturing techniques to lower the cost and time required to produce these treatments. Efforts are also underway to create “off-the-shelf” or allogeneic CAR T-cell therapies using cells from healthy donors. This would allow them to be produced in large batches, making them more readily available, safer, and effective against more cancer types.