Revolutionizing Cancer Care: The Evolution of Immuno-Oncology

Listicle 1 Revolutionizing Cancer Care: The Evolution of Immuno-Oncology Frances Gatta Immuno-oncology is rooted in the recognition of the immune system's potential to identify and destroy cancer cells while sparing healthy cells and establishing lasting immunity against recurrence.1 In 1891, William Bradley Coley, now recognized as the father of immunotherapy, started experimenting with using Streptococcal bacteria to help the immune system fight cancer after observing spontaneous remission in cancer patients with a streptococcal skin infection.2 In the 1980s, the availability of the hepatitis B vaccine, based on a single cell surface antigen, renewed hope in the potential of treating diseases like cancer with immunotherapy. In recent years, research efforts have led to significant advancements in immuno-oncology, as traditional treatments like surgery, chemotherapy and radiation therapy have shown limited efficacy, especially in treating advanced cancers. In this listicle, we explore some recent developments in the field. Oncolytic virus therapy Oncolytic virus therapy, which involves using viruses to treat cancer, has been around since the late 1800s to early 1900s but has only recently become well-developed and appreciated.3 Oncolytic viruses target and kill cancer cells by replicating in and spreading through the tumor. This therapy also works by reactivating the immune system and triggering an antitumor immune response. Additionally, oncolytic viruses can attack tumor-associated stroma cells, causing vascular collapse in the tumor.4 In 1991, oncolytic virus therapy gained momentum with the success of a herpes simplex virus (HSV) lacking the thymidine kinase (TK) gene in inhibiting the growth of human glioma xenografts. The field has since seen remarkable growth, leading to the regulatory approval of oncolytic HSV talimogene laherparepvec (T-VEC) for treating advanced melanoma in 2015. Many studies have shown the potential of oncolytic viruses in targeting cancer cells resistant to conventional treatments. However, obstacles such as inadequate oncolytic virus penetration and spread, host antiviral immunity, the presence of virus-resistant or virus-sensitive tumor cells and their limited efficacy as standalone treatments, limit their clinical application.5 Credit: iStock REVOLUTIONIZING CANCER CARE: THE EVOLUTION OF IMMUNO-ONCOLOGY 2 Listicle Researchers are now exploring combining oncolytic virus therapy with other immunotherapeutic agents, like immune checkpoint inhibitors, to address some of these challenges and develop a more effective cancer treatment plan.6 Another significant challenge is finding an efficient method to transport oncolytic viruses to tumor cells. Recent studies have shown promising results using nano vectors to deliver the virus into tumor cells.5 Cancer vaccines After over a century of research, developing cancer vaccines has proven to be a long journey.7 Factors like the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells and the potential for tumor escape mechanisms have limited progress.8 To date, only a small number of cancer vaccines – three therapeutic and four preventive – have been approved. Many others are in different phases of clinical trials.9 Cancer vaccines are designed to trigger the immune system to attack cancer cells.10 Their efficacy depends on the type of antigens used, the tumor microenvironment and the vaccine formulation, among other factors. The first successful preventative vaccines targeted viral infections linked to cancer development, including the human papillomavirus (HPV) and Hepatitis B virus (HBV).7 Currently, there are no approved vaccines for preventing non-viral cancers in humans. However, researchers have explored vaccines that target active cancers as a type of immunotherapy. These therapeutic cancer vaccines include the Bacillus Calmette-Guerin (BCG) vaccine for treating early-stage bladder cancer and Sipuleucel- T (Provenge) for treating castration-resistant prostate cancer.7 Progress in research on neoantigens, which are specific to tumor cells, has contributed to the advancement in cancer vaccines. Researchers are investigating the development of personalized vaccines that target these antigens in combination with immune adjuvants and immune-modulators for optimal immune response and cancer outcomes.10 Furthermore, efforts are being made to improve vaccine delivery methods and develop strategies to overcome immunosuppressive tumor microenvironment.11 Adoptive cell therapy Adoptive cell therapy (ACT), which uses a patient's engineered immune cells to treat cancer, has emerged as a game-changer in immuno-oncology. The three primary ACTs, tumor-infiltrating lymphocyte (TIL) therapy, T cell receptor (TCR) T-cell therapy and Chimeric antigen receptor (CAR) T-cell therapy, have existed for decades. However, CAR T-cell therapy's recent clinical and commercial success in treating hematological malignancies has brought ACT into the spotlight.7 The successful treatment of 6-year-old Emily Whitehead, who is leukemia-free to this day, using Kymriah (anti-CD19 CAR-T cells) in 2012 reignited interest in and pushed the development of CAR-T cell therapy. Today, eight CAR-T cell therapies have received regulatory approval globally.12 However, ACT has limitations that hinder its availability, accessibility and adoption. These limitations include high costs, complex manufacturing processes and risk of cytokine release syndrome, an inflammatory response in which immune cells rapidly release cytokines into the bloodstream. Hence, researchers are working to make these therapies more effective, safer, scalable and accessible. In addition to exploring their potential in treating other cancer types and diseases like HIV, researchers are investigating the benefits and safety of combining ACT with other cancer treatments like immune checkpoint inhibitors, chemotherapy and radiotherapy.13 REVOLUTIONIZING CANCER CARE: THE EVOLUTION OF IMMUNO-ONCOLOGY 3 Listicle Research into CAR-T cell therapy and ACT in general continues to advance, particularly in treating solid tumors, which present greater challenges than hematological malignancies. Researchers are working to broaden CAR-T targets to include other immune cells, including macrophages and NK cells, known for their anti-tumor properties.13 Cancer nanomedicine Over the last three decades, groundbreaking research in nanomedicine and the development of nanocarriers has risen, driven by advancements in nanotechnology and an improved understanding of cancer biology. 14 Cancer nanomedicine uses nanoparticles, typically 1 to 100 nanometers in size, to deliver anti-cancer drugs.15 It has shown the potential to improve cancer therapy by improving tumor targeting, increasing drug efficacy, reducing toxicity, modulating drug release, managing multidrug resistance, promoting immune regulation and facilitating drug delivery, among other advantages.16 Up to 15 cancer nanomedicines have been approved globally, with the first being Doxil, which received US Food and Drug Administration (FDA) approval in 1995 for treating ovarian cancer. Over 80 new cancer nanomedicines are being studied in more than 200 clinical trials. However, there have been no regulatory approvals for cancer nanomedicines that actively target tumor cells, and only 10 are being researched.14,17 Moreover, the introduction of cancer nanomedicines in clinical practice has slowed down, primarily due to their limited efficacy stemming from challenges overcoming physiological barriers to reach their target. Researchers aim to gain a deeper understanding of how cancer nanomedicines travel within the body and to develop technologies that can deliver treatments more precisely to tumors.14 Immune checkpoint inhibitors Immune checkpoint inhibitors (ICIs) block negative immune regulation to restimulate immune activity against cancer cells. Since the first ICI, an antibody targeting the cytotoxic T lymphocyte antigen 4 (CTLA4), named ipilimumab, was approved by the FDA in 2011, ICIs have initiated a monumental shift in cancer therapy.18 ICIs were only approved for treating unresectable advanced melanoma unresponsive to traditional therapy. However, significant strides in treatment efficacy, patient outcomes and applicability across many cancers over the last years have moved these drugs from second or third-line drugs to first-line treatments. ICIs are also now being used as part of combination therapies, including chemotherapy and targeted therapies. As of January 2024, the FDA had approved 11 checkpoint inhibitors.19,20 In spite of the success achieved so far, challenges to clinical adoption – including primary and acquired resistance to ICIs, low overall response rates and the risk of acute and chronic toxicity – mean that there is still a long way to go in making ICIs accessible and beneficial for all cancer patients. Researchers are working on increasing patient treatment options, such as by discovering novel and relevant biomarkers that predict the efficacy and safety of ICIs and identifying more immune checkpoint molecules.18 The recent progress in immuno-oncology treatments in research and clinical practice has brought about a new wave of optimism and encouraged efforts in the fight against cancer. Despite challenges such as immune-related adverse effects and high costs, these therapies are becoming more prominent as preferred options alongside traditional treatment methods such as chemotherapy. Additionally, ongoing clinical studies focused on novel cancer treatments are paving the way for the development of more effective, targeted and tolerable drugs. Increased funding and support for research into the immune system and cancer biology will further advance new and existing treatments, bringing us closer to a cancer-free reality. REVOLUTIONIZING CANCER CARE: THE EVOLUTION OF IMMUNO-ONCOLOGY 4 Listicle References: 1. Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012;23(Suppl 8):viii6-viii9. doi: 10.1093/annonc/mds256 2. Dobosz P, Dzieciątkowski T. The intriguing history of cancer immunotherapy. Front Immunol. 2019;10. doi: 10.3389/fimmu. 2019.02965 3. Hemminki O, dos Santos JM, Hemminki A. Oncolytic viruses for cancer immunotherapy. J Hematol Oncol. 2020;13(1):84. doi: 10.1186/s13045-020-00922-1 4. Zhang S, Rabkin SD. The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy?. Expert Opin Drug Discov. 2021;16(4):391-410. doi: 10.1080/17460441.2021.1850689 5. Volovat SR, Scripcariu DV, Vasilache IA, et al. Oncolytic virotherapy: A new paradigm in cancer immunotherapy. Int J Mol Sci. 2024;25(2):1180. doi: 10.3390/ijms25021180 6. Gujar S, Pol JG, Kumar V, et al. Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy. Nat Protoc. 2024;19(9):2540-2570. doi: 10.1038/s41596-024-00985-1 7. Grimmett E, Al-Share B, Alkassab MB, et al. Cancer vaccines: past, present and future; a review article. Discov Oncol. 2022;13:31. doi: 10.1007/s12672-022-00491-4 8. Kaczmarek M, Poznańska J, Fechner F, et al. Cancer vaccine therapeutics: Limitations and effectiveness—a literature review. Cells. 2023;12(17):2159. doi: 10.3390/cells12172159 9. Hargrave A, Mustafa AS, Hanif A, Tunio JH, Hanif SNM. Recent advances in cancer immunotherapy with a focus on FDA-approved vaccines and neoantigen-based vaccines. Vaccines (Basel). 2023;11(11):1633. doi: 10.3390/vaccines11111633 10. Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol. 2018;18(3):168-182. doi: 10.1038/nri.2017.131 11. Fan T, Zhang M, Yang J, Zhu Z, Cao W, Dong C. Therapeutic cancer vaccines: advancements, challenges and prospects. Sig Transduct Target Ther. 2023;8(1):1-23. doi: 10.1038/s41392-023-01674-3 12. Zhang P, Zhang G, Wan X. Challenges and new technologies in adoptive cell therapy. J Hematol Oncol. 2023;16(1):97. doi: 10.1186/s13045-023-01492-8 13. Du S, Yan J, Xue Y, Zhong Y, Dong Y. Adoptive cell therapy for cancer treatment. Exploration (Beijing). 2023;3(4):20210058. doi: 10.1002/EXP.20210058 14. Fan D, Cao Y, Cao M, Wang Y, Cao Y, Gong T. Nanomedicine in cancer therapy. Sig Transduct Target Ther. 2023;8(1):1-34. doi: 10.1038/s41392-023-01536-y 15. Xu M, Han X, Xiong H, et al. Cancer nanomedicine: Emerging strategies and therapeutic potentials. Molecules. 2023;28(13):5145. doi: 10.3390/molecules28135145 16. Giri PM, Banerjee A, Layek B. A recent review on cancer nanomedicine. Cancers (Basel). 2023;15(8):2256. doi: 10.3390/ cancers15082256 17. Joyce Nirmala M, Kizhuveetil U, Johnson A, G B, Nagarajan R, Muthuvijayan V. Cancer nanomedicine: a review of nano- therapeutics and challenges ahead. RSC Adv. 2023;13(13):8606-8629. doi: 10.1039/D2RA07863E 18. Meng L, Wu H, Wu J, et al. Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks. Cell Death Dis. 2024;15(1):1-26. doi: 10.1038/s41419-023-06389-5 19. Sun Q, Hong Z, Zhang C, Wang L, Han Z, Ma D. Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends. Sig Transduct Target Ther. 2023;8(1):1-26. doi: 10.1038/s41392-023-01522-4 20. Paul J, Mitchell AP, Kesselheim AS, Rome BN. Overlapping and non-overlapping indications for checkpoint inhibitors in the US. J Clin Oncol. 2024;42:11057-11057. doi: 10.1200/JCO.2024.42.16_suppl.11057 About the author: Frances Gatta is a freelance writer and content marketing consultant for healthcare and life sciences companies. Her work has appeared in Nature, HealthTech Magazine, MDLinx, Medical Marketing & Media, Forbes Health, WebMD, Healthline, Everyday Health and more. Sponsored by: