Tumor infiltrating lymphocytes TILs

To date, cellular and gene therapy products submitted to FDA have included clinical studies indicated for bone marrow marking, cancer, cystic fibrosis, AIDS, and inborn errors of metabolism and infectious diseases. Of the current active INDs approximately 78% have been sponsored by individual investigators or academic institutions and 22% have also been industry sponsored. In addition to the variety of clinical indications the cell types have also been varied. Examples include tumor infiltrating lymphocytes (TIL) and lymphocyte activated killer (LAK) cells, selected cells from bone marrow and peripheral blood lymphocytes, for example, stem cells, myoblasts, tumor cells and encapsulated cells (e.g., islet cells and adrenal chromaffin cells). 

Infusion of tumor-infiltrating lymphocytes (TIL) isolated from tumor samples and expanded in vitro with rIL2 resulted in a more efficient tumor reduction in animal models [19] and showed activity in clinical studies [20], A significant impediment to generating therapeutic TILs resides in the inherent... 

Much attention has been paid to the role of CD8 T cells in the immunotherapy of cancer due to the cytotoxic property of these cells, and a large number of MHC class I-restricted tumor antigens have been identified using tumor-reactive CD8 T cells from patients peripheral blood mononuclear cells (PBMCs) or tumor-infiltrating lymphocytes (TILs) [283,289,290]. 

In recent years, interest has focused on the role of cell-mediated immune response in melanoma. Specific cell-mediated responses may play a role in tumor regression, but the role of specific cells such as cytotoxic T lymphocytes (CTLs) is not fully understood. Tumor-infiltrating lymphocytes (TILs) have been shown in vivo and in vitro to possess antitumor reactivity. TILs contain a large number of mature tumor-specific lymphocytes and have been a target for manipulation in immunotherapeutic approaches for melanoma. 

Adoptive therapy attempts to overcome blocks to the efferent arm of the immune system by harvesting immune cells from the patient, manipulating them to activate them or otherwise increase their effectiveness and then re-infusing them to target the tumor. Classically, the cell types used have included peripheral blood mononuclear cells (PBMC), lymphokine-activated killer cells (LAK), tumor infiltrating lymphocytes (TIL), and cytotoxic lymphocytes (CTL). 

LDI low-dose interferon MAA melanoma-associated antigen NSAID nonsteroidalanti-inflammatory drug SPF sun protection factor TAA tumor-associated antigen TIL tumor-infiltrating lymphocyte UVA ultraviolet A UVB ultraviolet B... 

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