Cancer Immunotherapies: Transforming Treatment for Patients

Listicle 1 Cancer Immunotherapies: Transforming Treatment for Patients Alison Halliday, PhD Cancer is a devastating disease that claims millions of lives each year, with around 19.3 million new cases and nearly 10 million cancer deaths recorded in 2020 alone.1 The urgent need for effective treatments is clear, especially as the incidence of the disease is projected to rise to 28.4 million cases by 2040.1 For decades, surgery, chemotherapy and radiotherapy have been the mainstay of cancer treatment. While there have been dramatic improvements in survival for some cancers, there has been limited progress against others. As a result, there is a pressing need for innovative treatment modalities that can help improve outcomes for patients. Fortunately, recent advances in the understanding of how the immune system works and how cancers can evade destruction by immune cells have given rise to a new type of treatment called immunotherapy. The immune system plays a crucial role in protecting the body from diseases, including infections and cancer. However, cancer cells can evade immune detection or suppress the immune response. Immunotherapy aims to boost the immune system’s ability to find and destroy cancer cells by using substances that help boost the overall immune response or activate specific immune cells. In this listicle, we explore the different types of immunotherapies and how these approaches are revolutionizing cancer treatment, delivering remarkable outcomes for some patients. We also discuss the ongoing challenges that need to be overcome to fully unlock the transformative potential of these cancer treatments – offering the hope of improved survival and quality of life for more people with cancer. Immune checkpoint inhibitors The immune system has a system of “brakes” called immune checkpoints to prevent it from mounting an excessive response that could harm healthy cells and tissues. But cancer cells can sometimes manipulate these checkpoints, allowing them to evade destruction. Immune checkpoint inhibitors are drugs that work by blocking these immune checkpoints, effectively switching off the “brakes” on the immune system and enabling it to find and attack cancer cells. Over the past decade, immune checkpoint inhibitors have demonstrated a breakthrough in cancer treatment – with several now approved to treat a variety of different cancers.2 For example, one drug targets cytotoxic T lymphocyte-associated protein 4 (CTLA-4), a checkpoint protein found on the surface of T cells – a type of immune cell that plays a crucial role in the immune response to cancer. CANCER IMMUNOTHERAPIES: TRANSFORMING TREATMENT FOR PATIENTS 2 Listicle Other inhibitors target programmed cell death protein 1 (PD-1), another checkpoint protein found on T cells, or its partner programmed cell death ligand 1 (PD-L1), which is sometimes found at high levels on cancer cells to help them evade the immune response. Adoptive cell therapies In recent years, adoptive cell therapies have emerged as an exciting development in cancer treatment.3 The approach involves collecting the patient’s own immune cells, which are then either multiplied in the laboratory or modified to enhance their ability to target and kill the cancer cells, before putting them back into the body. There are several types of adoptive cell therapy, including: • Tumor-infiltrating lymphocyte (TIL) therapy: T cells extracted from the patient’s tumor are grown in large numbers in the lab and re-administered back to the patient. While TIL therapy has shown promising results for certain cancers like melanoma and breast cancer, it remains an experimental approach. • Chimeric antigen receptor T-cell (CAR T-cell) therapy: T cells are modified in the lab with CARs that can recognize specific proteins – or antigens – on the surface of cancer cells. The US Food and Drug Administration (FDA) has approved several CAR T-cell therapies for treating some types of blood cancer4 and researchers are exploring strategies to improve their effectiveness against solid tumors.5 • Engineered T-cell receptor (TCR) therapy: The patient’s T cells are engineered in the lab with receptors that can detect cancer-associated antigens displayed on the surface of tumor cells. In 2022, the first TCR therapy received FDA approval for a rare type of melanoma occurring in the eye.6 Researchers are also exploring adoptive cell therapies using immune cells from healthy donors to develop “off-the-shelf” treatments for cancer patients.7 Monoclonal antibodies Antibodies are proteins that are produced by immune cells to help combat infections. Monoclonal antibodies, also known as therapeutic antibodies, are created in the laboratory but mimic the function of natural antibodies. Like the body’s own antibodies, they are designed to identify and stick to a specific protein on the surface of cells. Several monoclonal antibodies have been approved to treat a wide variety of cancers, and these therapeutics are now considered to be a main component of cancer treatment.8 Some function as immunotherapies by activating the immune system to fight cancer. For example, they may attach themselves to cancer cells, facilitating recognition and destruction by immune cells – while others act on immune cells to help the immune system attack cancer cells. Other antibodies may work in a more targeted way, for example by blocking signals that stimulate cancer cells to divide. Oncolytic viral therapy Oncolytic viruses can infect and selectively kill cancer cells without harming healthy cells.9 These viruses can occur naturally or can be made in the laboratory by modifying existing viruses. CANCER IMMUNOTHERAPIES: TRANSFORMING TREATMENT FOR PATIENTS 3 Listicle Researchers are investigating the potential of using oncolytic viruses to treat cancer, either alone or in combination with other treatments such as chemotherapy or radiotherapy. For many years, oncolytic viruses were considered tools for directly killing cancer cells. However, emerging evidence suggests that some of these viruses may also work as immunotherapies, stimulating the patient’s immune system to find and destroy other cancer cells. In 2016, Talimogene laherparepvec (T-VEC) was the first oncolytic viral therapy to receive FDA approval to treat advanced melanoma skin cancer.10 T-VEC is derived from the herpes simplex virus type 1, commonly associated with cold sores. Treatment vaccines Cancer treatment vaccines are designed to help the immune system recognize and react to tumorassociated antigens.11 Researchers are investigating several different types of therapeutic vaccines, including those made from whole cancer cells, proteins or protein fragments, pieces of DNA or RNA or immune cells. In 2011, Sipuleucel-T was the first therapeutic cancer vaccine to be approved by the FDA as a treatment for some men with advanced prostate cancer.12 Immune system modulators Immune system modulators can boost the body’s immune response against cancer. They work by targeting specific components of the immune system or have a broader effect. Examples include: • Interleukins: These are a type of cytokine, a protein made by some immune cells to regulate the immune response. A man-made version of interleukin-2 (IL-2) is approved to treat advanced kidney cancer and melanoma.13 • Interferons: These are also cytokines that help make immune cells more active against cancer. IFN-a is approved to treat cancers including leukemia, sarcoma, lymphoma and melanoma.14 • Immunomodulators: These treatments help stimulate the immune system to react to cancer. They include thalidomide, lenalidomide, pomalidomide – which induces IL-2 release and inhibits tumor blood vessel formation – and imiquimod, a topical cream that triggers cells to release cytokines. And for many decades, Bacillus Calmette-Guérin (BCG), a live weakened strain of Mycobacterium bovis used to prevent tuberculosis, has also been used as an immunotherapy for bladder cancer.14 Future perspectives Cancer immunotherapy represents a new paradigm in cancer care. The approach is already transforming the lives of some patients – and holds immense promise for the future of cancer treatment. However, several challenges will need to be overcome to bring the benefits of immunotherapy to all cancer patients. Many tumors don’t respond well enough to immunotherapy, or the cancer develops resistance and begins to grow and spread. These treatments can also cause side effects, many of which occur because the activated immune system also attacks healthy tissues. Additionally, the high cost of certain immunotherapies can limit their accessibility to patients. CANCER IMMUNOTHERAPIES: TRANSFORMING TREATMENT FOR PATIENTS 4 Listicle Nevertheless, combining immunotherapeutic agents with other treatments like chemotherapy, radiotherapy or targeted therapies has shown promising results in clinical trials. As these treatments all work in different ways, such combination strategies offer the potential to eliminate cancer permanently. Identifying biomarkers that can accurately predict which patients will respond to immunotherapy is also a major area of research. Personalizing treatment based on a patient’s unique genetic and immunological profile also offers the promise of more targeted and effective immunotherapies. Gaining a better understanding of how cancer cells evade the immune system could lead to the development of next-generation immunotherapies. 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