Tumour-infiltrating lymphocyte therapy landscape: prospects and challenges

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Tumour-infiltrating lymphocyte (TIL) therapy represents a significant advancement in adoptive cell transfer for solid tumours.
• The accelerated approval of lifileucel by the FDA highlights the growing clinical relevance of TIL therapy.
• This review synthesizes the current understanding of TIL therapy, encompassing its history, biological underpinnings, and clinical impact.

Purpose of the Study:

• To provide a comprehensive review of tumour-infiltrating lymphocyte (TIL) therapy.
• To examine the historical development, biological mechanisms, clinical efficacy, safety, and limitations of TIL therapy.
• To explore advancements in TIL manufacturing and emerging strategies to overcome current challenges.

Main Methods:

• Comprehensive literature review of TIL therapy.
• Analysis of historical data, clinical trial outcomes, and biological studies.
• Examination of manufacturing techniques, genetic modifications, and novel therapeutic approaches.

Main Results:

• TIL therapy has shown promise in treating solid tumours, with lifileucel's recent FDA approval marking a key milestone.
• Advancements in TIL manufacturing, including novel culture techniques and automation, aim to improve scalability and effectiveness.
• Challenges persist, including high-dose interleukin-2 toxicity, complex manufacturing, and tumour immune evasion.

Conclusions:

• Emerging strategies such as checkpoint inhibitor combinations, engineered TILs, and metabolic reprogramming are being developed to enhance TIL efficacy.
• TIL therapy holds significant potential to improve existing cancer immunotherapy approaches.
• Continued research and development are crucial for optimizing TIL therapy's clinical application and overcoming its limitations.