Is Immunotherapy the Cure to Cancer?

The immune system fights illness, sicknesses, viruses, and common infections, but what if it could fight cancer? This is the central basis of immunotherapy; The immune system is stimulated to fight cancer in the body. Why couldn’t the immune system fight cancer already, and what makes immunotherapy so unique? The immune system can detect cancerous cells in the body, but it is not strong enough to kill them because the cancerous cells may hinder the immune system's response to fighting back or even hide away from the immune system. Immunotherapy assists the immune system by enhancing its ability to target and destroy cancer cells, making it a transformative approach to cancer treatment. Unlike traditional therapies like chemotherapy and radiation, which indiscriminately kill both cancerous and healthy cells, immunotherapy uses the body’s own defense mechanisms, providing a more targeted and potentially less harmful approach (Cancer Research UK, 2023).

One of the most groundbreaking developments in immunotherapy is checkpoint inhibitors. These drugs target immune checkpoints, molecules on immune cells that need to be activated (or inactivated) to start an immune response. Tumor cells exploit these checkpoints to avoid being attacked by the immune system. The first breakthrough came with the FDA approval of ipilimumab, a checkpoint inhibitor that targets CTLA-4, in 2011 for treating metastatic melanoma (Topalian et al., 2015). This marked the beginning of a new era in cancer treatment. Recent developments have led to newer checkpoint inhibitors like nivolumab and pembrolizumab, which can treat various cancers, including lung, kidney, and bladder cancer (Weber et al., 2017). Checkpoint inhibitors significantly improve patient outcomes; for example, patients with advanced melanoma treated with pembrolizumab have shown a five-year survival rate of 34%, a remarkable improvement compared to traditional therapies (Robert et al., 2015). However, checkpoint inhibitors can cause immune-related adverse effects, including colitis, pneumonitis, and hepatitis, as the boosted immune system may attack healthy tissues (Weber et al., 2017).

CAR-T (Chimeric Antigen Receptor T-cell) therapy is another method that involves genetically engineering a patient's T-cells to better recognize and attack cancer cells. Initially developed in the early 2000s, CAR-T therapy gained FDA approval in 2017 for treating pediatric leukemia (Maude et al., 2018). Recent advancements in CAR-T technology include improved cell engineering techniques, such as dual-targeting CAR-T cells, which can recognize multiple antigens on cancer cells, reducing the chances of relapse (Martinez et al., 2021). CAR-T therapy has shown good efficacy as clinical trials report complete remission rates as high as 83% for pediatric acute lymphoblastic leukemia patients treated with tisagenlecleucel (Maude et al., 2018). These therapies provide hope to patients who have used all other treatment options. However, CAR-T therapy has challenges with severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity. (Neelapu et al., 2018). Therefore, researchers are investigating ways to improve CAR-T cell persistence.

Future directions in immunotherapy reveals benefits in the combination of therapies. For example, combining checkpoint inhibitors with chemotherapy, radiation, or other immunotherapies has shown promise in enhancing treatment efficacy. Research suggests that combinations can provide synergistic effects, improving patient responses even in cancers previously resistant to treatment (Weber et al., 2017). Immunotherapy is also being explored for a broader range of cancers. While therapies like CAR-T have been most successful in treating blood cancers, researchers are working to adapt these therapies for solid tumors, such as breast, pancreatic, and prostate cancer (Martinez et al., 2021). As immunotherapy continues to advance, ethical and economic considerations must be addressed. The high cost of these therapies raises questions about access and equity, particularly in low- and middle-income countries. Additionally, the long-term effects of immune system manipulation are still not fully understood.

Immunotherapy has revolutionized cancer treatment, giving hope to patients who previously had limited options. From checkpoint inhibitors to CAR-T therapy, these therapies have significantly improved patient outcomes and cancer care. The future of immunotherapy is promising as we continue to develop combination therapies, and tackle challenges such as managing side effects, improving access, and expanding applications to solid tumors. With continued research and innovation, immunotherapy could one day become the cure to many forms of cancer.

Refrences

“What Is Immunotherapy?” What Is Immunotherapy| Cancer Research UK, 24 Sept. 2024, www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/what-is-immunotherapy/#:~:text=Immunotherapy%20uses%20our%20immune%20system,for%20other%20types%20of%20cancer.

Martinez, M., Moon, E. K., & June, C. H. (2021). CAR-T cells for solid tumors: New strategies and novel antigens. Clinical Cancer Research, 27(8), 1879-1886. doi:10.1158/1078-0432.CCR-20-3888

Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., ... & Grupp, S. A. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. The New England Journal of Medicine, 378(5), 439-448. doi:10.1056/NEJMoa1709866

Neelapu, S. S., Locke, F. L., Bartlett, N. L., Lekakis, L. J., Miklos, D. B., Jacobson, C. A., ... & Rossi, J. M. (2018). Axicabtagene ciloleucel CAR-T cell therapy in refractory large B-cell lymphoma. The New England Journal of Medicine, 377(26), 2531-2544. doi:10.1056/NEJMoa1707447

Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., ... & Wolchok, J. D. (2015). Pembrolizumab versus ipilimumab in advanced melanoma. The New England Journal of Medicine, 372(26), 2521-2532. doi:10.1056/NEJMoa1503093

Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2015). Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nature Reviews Cancer, 16(5), 275-287. doi:10.1038/nrc.2016.36

Weber, J. S., D’Angelo, S. P., Minor, D., Hodi, F. S., Gutzmer, R., Neyns, B., ... & Robert, C. (2017). Nivolumab versus chemotherapy in patients with advanced melanoma who had progressed after anti-CTLA-4 treatment (CheckMate 037): A randomized, controlled, open-label, phase 3 trial. The Lancet Oncology, 16(4), 375-384. doi:10.1016/S1470-2045(15)70076-8

Image Refrence

“Anti-Cancer Immunotherapy: A Smart Approach.” Biotherapy International, 24 Sept. 2024, ibiotherapy.com/immunotherapy/.