Tumor-infiltrating lymphocytes (TILs), which include B-cells, T-cells, and natural killer (NK) cells, are an important component in anti-tumor immune responses. TILs involve the use of special immune cells called T-cells, a type of lymphocyte or white blood cell. Lymphocytes protect the body from viral infections, help other cells fight bacterial and fungal infections, produce antibodies, fight cancers, and coordinate the activities of other cells in the immune system.
Some tumors are highly infiltrated by immune cells, while only subtle infiltrations are detectable in others. In general, an increased number of immune cells correlates with a favorable clinical outcome in various malignancies, such as melanoma, colorectal, lung and breast cancers. TILs may offer a new target for cancer immunotherapy – to allow the precise killing of cells through tumor antigen recognition – and may also serve as a prognostic biomarker in a variety of cancers.
TILs express a variety of different antigens on their cell membrane including CD3, CD4, CD8, CD16, CD20, CD56 and CD57, CD68, CD169 and FOXP3, to regulate the immune system and to suppress tumor growth (Table 1). Several studies have demonstrated that upregulation of immune checkpoint (CP) proteins such as PD-1, CTLA-4, Tim-3 and LAG-3, can lead to TILs exhaustion and tumor progression, whereas blockade of CP proteins suppresses tumor growth, increases glucose uptake in TILs and reinvigorates their function.
Chapter 1 The Emergence of Cell Therapy Using TILs
Chapter 2 Development of TIL Therapies in Metastic Melanoma
TIL Generation Explained
Importance of Lymphodepletion
Role of Interleukin-2
Feasibility of TIL as a Mainstream Treatment Option
Chapter 3 Development of TIL Therapies in Other Tumour Types
Head and Neck Cancers
Chapter 4 Clinical Development of TIL Therapies
Lifileucel (LN-144), Iovance Biotherapeutics
LN-145, Iovance Biotherapeutics
TILT-123, TILT Biotherapeutics
Optera Therapeutics Corp.
Other Centers Conducting TIL Research
Future Perspectives for TIL
Chapter 5 References
Table 1 : TILs and Tumor Specific Antigens
Table 2 : Adoptive T-Cell Therapy (ATC) Cellular Therapies
Table 3 : Clinical Trials Studying TIL Therapies
Figure 1 : Generation of Tumor Infiltrating Lymphocytes
Figure 2 : IL-2 Signaling Pathways and their Primary Biological Effects in Different Immune Cell Types
Figure 3 : TILT Biotherapeutics Development Pipeline
Tumor-specific Antigen are compounds that are produced in tumor cells. These cells trigger an immune response in the host. Tumor Antigen are not membrane proteins, but cytosolic protein derivatives. TumorView Report
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