Revolutionising cancer care, CAR-T therapy offers hope for aggressive haematological malignancies and shows promising results in treating solid tumours.
Introduction: Revolutionising Blood Cancer Treatment with CAR-T Therapy
Blood cancers, or haematological malignancies, are aggressive cancers and are often fatal when diagnosed at a late stage. Despite a global increase in these cancers, survival rates have seen a significant boost. This uptick is due to advancements in treatments, including the development of effective chemotherapy and targeted therapies. Cell therapies such as Chimeric Antigen Receptor (CAR) T-cell (CAR-T) therapy have emerged as game-changers among these targeted therapies. Traditionally, CAR-T therapy has been employed to treat blood cancers. However, new research has shown promising results for its application in treating solid tumours, particularly glioblastoma. In this article, we will delve into what CAR-T therapy is and explore the significance of this new research. Additionally, the article will discuss how healthcare professionals can guide cancer patients about CAR-T therapy.
Understanding CAR-T Therapy
CAR-T therapy has been revolutionary as it has yielded remarkably effective and long-lasting clinical responses. The process involves obtaining the patient’s T cells, which are natural immune system white blood cells that help fight and protect against germs. In the lab, these cells are modified to include a synthetically generated chimeric antigen receptor on the surface of the T cells. The receptors specifically target the cancer cells. After infusing the modified cells into the patient’s bloodstream, these modified T cells can recognise, target, and attack cancer cells.
CAR-T therapy has been approved for blood cancers such as multiple myeloma, some leukaemias, and B-cell lymphoma. Six CAR-T treatments have been authorised in the US and have shown effective clinical responses. For instance, 98% of patients responded to cilia-cell therapy, and 78% showed a complete response of having no more cancer cells. Because of the advancements in CAR-T treatments for haematological malignancies, five-year survival rates have significantly increased. Different lymphomas showed significant improvement during various large-scale trials when treated with CAR-T therapies. 40–54% of patients with aggressive B cell lymphoma, 67% of patients with mantle cell lymphoma, and 69–74% of patients with indolent B cell lymphomas have completely obliterated their cancers. Overall, CAR-T cell therapies have become an important treatment option for late-stage blood cancers, and these therapies are starting to be considered for use earlier in the treatment process instead of just as a last resort.
Solid Tumours and CAR-M Therapy
In the past, CAR-T therapy faced challenges when it came to treating solid tumours, so its application is primarily approved and used for late-stage blood cancers. Then, researchers developed CAR-macrophages (CAR-M) therapy as the potential solution to overcome the challenges CAR-T therapy faced in treating solid tumours. Instead of the patient’s T cells, macrophages are extracted, modified, and reintroduced into the patient. The modified macrophages target and engulf cancer cells and also release cytokines and chemokines, which create a pro-inflammatory environment within the solid tumour. Recently, CellOrigin Biotechnology, a company in China, has dosed its first patient with CAR-M in its clinical trial, and results suggest that the product is safe and has no dose-limiting toxicity. This innovative approach holds promise for improving outcomes in solid tumour treatment.
Breaking Barriers: CAR-T Therapy in Solid Tumours
Concurrently, researchers are continuously refining CAR-T therapy to target solid tumours effectively. In a recent breakthrough reported in the New England Journal of Medicine last month, a group at Harvard developed a variation of CAR-T therapy that uses CARv3-TEAM-E T cells to target a molecule known as EGFRv3 and another form known as “wild” EGFR, which are found in glioblastoma. In addition to targeting glioblastoma-specific cancer cells, these modified T cells also recruit nearby T cells to fight the cancer. The study involved three patients, all of whom showed significant tumour shrinkage, although two were transitory. Remarkably, one patient had a tumour shrink by more than 60%, and it persisted for more than 150 days after the infusion.
This study is significant as glioblastoma, the most aggressive primary brain tumour, has a poor prognosis for recurrent disease and has no effective treatment options. Despite decades of research, treatments for glioblastoma have also seen little progress. Therefore, while the study is small and two out of three patients’ tumour shrinkage was transient, it is a significant step forward. It demonstrates the potential of CAR-T therapy in effectively targeting solid tumours, offering a promising new approach in the battle against aggressive tumours.
CAR-T Therapy Across Asia: Advancements and Adoption
CAR-T therapy is offered as a last resort for certain blood cancers in several Asian countries such as Singapore, Malaysia, China, Japan, and South Korea. In Singapore, CAR-T cell therapy with Kymriah received approval in 2021 for treatment for children and young people up to the age of 25 who have relapsed or not responded to therapy for acute lymphoblastic leukaemia, and adults with diffuse large B cell lymphoma, transformed follicular lymphoma, or primary mediastinal B cell lymphoma who have relapsed or not responded to initial treatment.
In Malaysia, the Malaysian Genomics Resource Centre Bhd (MGRC) aims to make CAR-T treatments more affordable compared to prices in Europe and the US. China’s National Medical Products Administration (NMPA) has granted approval for several CAR-T therapies and has over 700 registered CAR-T clinical trials, emerging as a strong global leader in CAR-T research. In Japan, Abecma is approved for adults with relapsed or refractory multiple myeloma who have received at least three prior therapies. South Korea has two approved CAR-T therapies, Kymriah and Carvykti. However, authorities have recently issued stricter guidelines to monitor for side effects in these approved therapies.
Navigating CAR-T Therapy: A Guide for Healthcare Professionals
While CAR-T therapy may still be in its early stages in Asia, the rapid advancements and commitment to research signal a promising future for this groundbreaking treatment. As healthcare professionals play an important role in cancer patient’s journey, here are ways they can help if CAR-T therapy becomes an option:
- Assessing Suitability: Given that most countries resort to CAR-T treatments as a last line of defence, it is crucial to assess patient eligibility. For example, patients with intracranial hypertension, respiratory failure, disseminated intravascular coagulation, or haematosepsis may not be eligible.
- Educating Patients: Discuss the process this treatment with patients, outlining the collection, reprogramming, and reinfusion of T cells and the potential benefits and risks associated with it so that they can make informed decisions. Risks include common side effects such as Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome, which are highly treatable and can be managed.
- Managing Expectations and Monitoring: Healthcare professionals also need to manage patients’ expectations as responses to the therapy can vary. Patients also need to be closely monitored for any adverse complications.
- Support and Counselling: Dealing with cancer is daunting, and patients undergoing CAR-T therapy may require additional psychological support. It is crucial to facilitate assistance from other professionals, such as psychologists or counsellors, and involve the family to form a comprehensive support network.
Embracing Hope: The Future of Cancer Treatment
In conclusion, CAR-T therapy represents a revolutionary breakthrough in cancer treatment, offering hope to patients with aggressive haematological malignancies. The remarkable efficacy demonstrated in treating late-stage blood cancers underscores its transformative potential, as evidenced by significantly improved survival rates and promising clinical responses. Moreover, recent breakthroughs in targeting solid tumours, particularly glioblastoma, highlight the expanding horizons this therapy beyond its traditional applications. With continued research and collaboration, CAR-T therapy holds the promise of transforming the landscape of cancer treatment and offering renewed hope to patients worldwide.
References
- Zhang, N., Wu, J., Wang, Q., et al. (2023). Global burden of hematologic malignancies and evolution patterns over the past 30 years. Blood Cancer Journal, 13(82). https://doi.org/10.1038/s41408-023-00853-3
- Lei, A., Yu, H., Lu, S., et al. (2024). A second-generation M1-polarized CAR macrophage with antitumor efficacy. Nature Immunology, 25, 102–116. https://doi.org/10.1038/s41590-023-01687-8
- Choi, B. D., Gerstner, E. R., Frigault, M. J., Leick, M. B., Mount, C. W., Balaj, L., Nikiforow, S., Carter, B. S., Curry, W. T., Gallagher, K., & Maus, M. V. (2024). Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. The New England Journal of Medicine, 390(14), 1290-1298. https://doi.org/10.1056/NEJMoa2314390
- Sheykhhasan, M., Ahmadieh-Yazdi, A., Vicidomini, R., et al. (2024). CAR T therapies in multiple myeloma: unleashing the future. Cancer Gene Therapy. https://doi.org/10.1038/s41417-024-00750-2
- Cappell, K. M., & Kochenderfer, J. N. (2023). Long-term outcomes following CAR T cell therapy: what we know so far. Nature Reviews Clinical Oncology, 20, 359–371. https://doi.org/10.1038/s41571-023-00754-1
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