What Is Chemotherapy and Immunotherapy?
Chemotherapy is the most commonly used treatment for cancer. In this therapy, drugs kill cancer cells and prevent tumor growth by interfering with cell division. Various chemotherapy drugs are available, which can be used alone or combined with multiple drugs to treat various cancers.
Chemotherapy drugs are usually given intravenously (through a vein), and the drug's action is not specific; it works throughout the body. Chemotherapy may also be paired with other cancer therapies, such as surgery or radiation therapy. Since the treatment is designed to destroy all rapidly dividing cells, it can also affect some fast-growing healthy cells and cause side effects like hair loss.
Immunotherapy is a cancer treatment that helps the immune system fight against cancer. The immune system comprises white blood cells (WBC), organs, and tissues of the lymph system that help the body fight against infections and other diseases. Cancer usually gets around many of the immune system's natural defenses, making cancer cells continue to grow. Immunotherapy works by training the immune system to identify and kill cancer cells.
It also helps produce cancer-fighting immune cells that effectively trace and destroy cancer cells. Different types of immunotherapy include monoclonal antibodies and immune checkpoint inhibitors, T-cell therapy, non-specific immunotherapies, oncolytic virus therapy, and cancer vaccines. While immunotherapy has shown remarkable success in some patients, it is not universally effective, and resistance can develop over time.
How Does Chemo-Immunotherapy Combination Work?
Chemo-immunotherapy brings a fundamental change in the traditional cancer treatment. Instead of viewing chemotherapy and immunotherapy as mutually exclusive, this approach combines their strengths to create a synergistic effect. The rationale behind this chemo-immunotherapy is that immunotherapy can eliminate cancer that has spread to a distant part of the organ or body. At the same time, it is less effective in destroying a solid tumor mass.
Chemotherapy can enhance the efficacy of immunotherapy because it can remove all or most of the tumor substance in the primary tumor mass. Thus decreasing the cell numbers that should be killed by immune cells and reducing the immunosuppressive factors produced by cancer cells. Additionally, a few chemotherapy drugs may directly stimulate antitumor immunity, which may be particularly beneficial for tumors with low effector T cell infiltration surrounding the tumor.
The following is how the chemo-immunotherapy works:
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Chemotherapy is provided to reduce the tumor burden. This process helps reduce the physical and metabolic stress tumors impose on the immune system.
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Chemotherapy drugs can change the body's immune response, such as by promoting the release of antigens or danger signals from dying tumor cells. These signals stimulate the immune system, making it more attentive.
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Immunotherapy can work more effectively with reduced tumor burden and the immune system preparing for work.
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Successful chemo-immunotherapy can lead to immune memory, which means the immune system remembers the cancer cells and can continue to fight them even after treatment has ended, providing a durable response.
What Are the Uses of Chemo-Immunotherapy?
Chemo-immunotherapy is now being used for different types of cancer and has also shown remarkable promise across these cancer types.
Here are some notable examples of its applications:
Lung Cancer - Chemo-immunotherapy combination for non-small cell lung cancer was approved in 2017. The method used a combination of the immunotherapy drug, Pembrolizumab, with the two chemotherapy drugs, Carboplatin and Pemetrexed, which has been proven to be safe and more effective than only chemotherapy. Nowadays, many other combinations have been used to treat lung cancer, and several clinical trials have been conducted to produce effective combinations.
Breast Cancer - The immunotherapy results in breast cancer individuals have been disappointing as they are not very effective in breast cancer. However, combining chemotherapy and immunotherapy has proven effective, especially in metastatic triple-negative breast cancer (TNBC). Combining immunotherapy drugs, Pembrolizumab, and chemotherapy like Paclitaxel protein-bound or Gemcitabine plus carboplatin has been shown to be more effective than chemotherapy alone.
Lymphoma - Lymphomas are generally treated with combinations of cancer treatments. Chemo-immunotherapy has long been used as a standard treatment for different types of lymphomas. The drug, Polatuzumab vedotin-piiq, in combination with the chemotherapy drug Bendamustine and a Rituximab medication, has been proven effective for various challenging lymphomas.
Melanoma - Melanoma is a highly aggressive skin cancer. It has been a pioneering area for immunotherapy. Combining chemotherapy with anti-PD-1 checkpoint and multi-peptide vaccine is beneficial for advanced melanoma.
Gastrointestinal Cancer - Multiple clinical trials have shown the efficacy of chemo-immunotherapy in gastrointestinal tumors. A combination of Pembrolizumab, 5-Fluorouracil, and Cisplatin reduces the death rate and disease progression in patients with advanced or metastatic gastroesophageal junction carcinoma. Nivolumab with chemotherapy has proven to be highly efficacious for advanced gastric, esophageal, or gastroesophageal junction adenocarcinomas or advanced or metastatic esophageal squamous cell carcinoma.
Bladder Cancer - For patients with advanced bladder cancer, chemo-immunotherapy has demonstrated promising results in clinical trials. Drugs like Pembrolizumab combined with platinum-based chemotherapy have led to improved outcomes.
What Are the Challenges of Chemo-Immunotherapy?
While chemo-immunotherapy has shown promising results in different types of cancer, it also has many challenges:
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The chemo-immunotherapy combination can lead to increased toxicity. Management of such side effects is very important or can lead to severe complications, and not all patients may tolerate the combination well.
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Similar to single-agent immunotherapy, chemo-immunotherapy can also develop resistance. Research is being conducted to understand the resistance mechanisms and develop strategies to overcome them.
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Identifying the correct patients for chemo-immunotherapy is pivotal. Predictive factors and biomarkers are studied to determine who will benefit most from this approach.
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Immunotherapy drugs can be expensive, and so can the combination of chemo-immunotherapy. The overall cost of treatment can be a significant burden for patients.
Conclusion
Chemo-immunotherapy is a combination approach of chemotherapy and immunotherapy to treat cancer. The strengths of both chemotherapy and immunotherapy create a powerful synergy. Many clinical trials are conducted across various cancer types, suggesting that chemo-immunotherapy combinations can improve outcomes for a broad spectrum of patients. However, there are many challenges and side effects to this therapy. As research continues, chemo-immunotherapy will likely play an increasingly vital role in cancer treatment, offering hope to patients and clinicians alike.
