Regulatory Landscape and Challenges in CAR-T Cell Therapy Development and Clinical Trials
摘要
Over last few decades, there has been a consistent increase in cancer burden globally, with ~20 million new cases annually, highlighting the need for effective, novel, and targeted immunotherapeutic approaches. To this end Chimeric Antigen Receptor T-cell (CAR-T) therapy emerged as an adoptive cell-based approach transforming treatment modality for various hematologic malignancies. This technique utilizes T lymphocytes tailored against cancer cells in a targeted manner and has delivered promising preclinical and clinical outcomes. This is a promising approach for the detection of malignant cells which otherwise escape immune surveillance and/or develop chemo/radio resistance. Several challenges viz. Cytokine Release Syndrome (CRS), neurotoxicity, and others, largely compromise the efficacy of such a targeted adoptive cell treatment. Additionally, lengthy and costly processes, scalability, and manufacturing issues compromise clinical utility and availability of this immunotherapy. This warrants for awareness on the current regulatory landscape surrounding CAR-T therapy, focusing on distinct frameworks for the approval in different jurisdictions at the global and national level. Here, we summarize leads obtained in this direction while discussing safety concerns, economic feasibility, manufacturing protocols, product standardization, and clinical trials designs—especially in context of efficacy and ethical considerations. Addressing these complex issues could streamline existing regulatory framework toward expediting CAR-T development, ultimately facilitating implementation in healthcare settings.