What is immunotherapy?
Immunotherapy is an innovative approach to fighting cancer. It harnesses the power of the body's immune system to find and destroy cancer cells. Unlike chemotherapy or radiation, which directly attack cancer cells, immunotherapy strengthens the immune system to combat the malignancy better. This therapy can either motivate the immune system to work harder or supply it with synthetic components, like monoclonal antibodies or immune checkpoint inhibitors, to target cancer cells more effectively. By bolstering the body's natural defenses, immunotherapy provides a groundbreaking way to treat cancer.
Background and first therapeutic agent
The idea of using the body's defense mechanisms to fight cancer has been around for a long time. In the late 1800s, an American surgeon named William Coley noticed that some cancer patients who developed bacterial infections experienced tumor shrinkage. This suggested that the immune system could be harnessed to attack cancer cells.
However, immunotherapy genuinely advanced in the 1990s with the development of particular proteins called cytokines, which help regulate the immune response. One such cytokine, interleukin-2, was approved by the FDA for treating kidney cancer and melanoma. This represented a significant breakthrough, as interleukin-2 can stimulate the growth and activity of T-cells, which are critical immune cells that can recognize and destroy cancer cells.
Modern spectrum of immunotherapeutic medications and indications
Today, immunotherapy encompasses a diverse range of therapies, each designed to target specific types of cancer [National Cancer Institute, 2019]. Here is an overview of the major categories of immunotherapeutic agents and their respective indications:
Immune checkpoint inhibitors are drugs that prevent cancer cells from deactivating immune cells. Some notable examples include pembrolizumab, nivolumab, and atezolizumab.
Pembrolizumab is approved for treating melanoma, lung cancer, head and neck cancers, and more. It works by blocking the PD-1 protein on T-cells, allowing them to more effectively attack cancer cells.
Nivolumab, also known as Opdivo, is often used for advanced melanoma, lung cancer, and bladder cancer. Like Pembrolizumab, it inhibits the PD-1 pathway, empowering the immune system to combat the cancer better.
Atezolizumab targets the PD-L1 protein, which helps tumors evade the immune response. This drug is utilized for urothelial carcinoma and non-small cell lung cancer, providing another avenue for the body's defenses to recognize and eliminate the malignant cells.
Monoclonal antibodies are lab-made proteins that can identify cancer cells, making it easier for the immune system to locate and eliminate them. For example, trastuzumab is used to treat HER2-positive breast cancer by marking these cancer cells, allowing the immune system to recognize and destroy them more effectively. Another drug, rituximab, is employed to manage B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. This monoclonal antibody targets the CD20 protein found on the surface of cancerous B cells, enabling the body's defenses to better identify and attack these malignant cells.
Cancer Vaccines help the immune system recognize and fight cancer cells. Sipuleucel-T for prostate cancer is an example, as it stimulates the body's immune response against a protein found in prostate cancer cells.
CAR T-cell therapy involves modifying a patient's T-cells to target and destroy cancer cells. From this group, axicabtagene ciloleucel is an approved therapy for certain types of large B-cell lymphomas.
The choice of immunotherapy depends on the specific type and stage of cancer. For advanced melanoma, immune checkpoint inhibitors like pembrolizumab and nivolumab have demonstrated impressive response rates. In non-small cell lung cancer, immunotherapy has become a standard treatment, with PD-1 inhibitors significantly improving survival rates. Additionally, drugs such as atezolizumab are now used as second-line therapies for bladder cancer. This leads to a noteworthy increase in the overall response rate, typically between 15% and 21% [American Cancer Society, 2024].
Immunotherapy for early- and late-stage cancers
For some early-stage cancers like melanoma and lung cancer, immunotherapy may be used after surgery to reduce the risk of the cancer returning. Checkpoint inhibitors are often used to eliminate any remaining cancer cells. The recurrence-free survival rate with nivolumab in melanoma is around 70% after one year.
For patients with advanced or relapsed cancers, immunotherapy provides new hope. Checkpoint inhibitors have improved overall survival in lung, bladder, and melanoma cancers. CAR T-cell therapy has also shown impressive results, leading to complete remission in 40-60% of patients with difficult-to-treat B-cell lymphomas.
What's next? Novel options in immunotherapy
Exciting new developments are happening in immunotherapy research. Some of the novel approaches being explored include:
- Bispecific antibodies are specially designed antibodies engineered to simultaneously target two markers - one on the cancer cell and one on the immune cell. The goal is to enhance the immune system's ability to recognize and destroy cancer cells more effectively. For instance, blinatumomab is a bispecific antibody currently being investigated for treating acute lymphoblastic leukemia.
- Oncolytic virus therapy utilizes viruses to directly infect and kill cancer cells while stimulating the patient's immune system. A notable example is talimogene laherparepvec, a modified herpes virus that has demonstrated promise in treating advanced melanoma, leading to complete responses in 16% of patients.
- Neoantigen vaccines are personalized vaccines designed to activate the immune system against the unique genetic mutations in an individual patient's cancer cells. These highly targeted neoantigen vaccines are still in clinical trials but represent an exciting frontier in immunotherapy with the potential to revolutionize cancer treatment.
Post-treatment prognosis after immunotherapy
Immunotherapy has significantly improved outcomes for many cancer patients, especially those with advanced disease. While individual responses vary, the benefits can be substantial.
Thus, in advanced melanoma, checkpoint inhibitors like pembrolizumab have increased 5-year survival rates from 10% to over 30% in some studies. Meanwhile, in non-small cell lung cancer, adding immunotherapy to standard treatments can boost 5-year survival rates to 25%, compared to just 5% with chemotherapy alone.
However, immunotherapy is not without challenges. Some patients experience manageable immune-related side effects, such as inflammation of the lungs, liver, or thyroid. However, severe cases may require discontinuing treatment [Lancet Oncology, 2024].