page_title: Tumor-infiltrating lymphocytes
section_title: Process
hierarchical_section_title: Tumor-infiltrating lymphocytes / Use in adoptive T cell transfer therapy / Process
caption_attribution_description: English: Cancer specific T-cells can be obtained by fragmentation and isolation of tumour infiltrating lymphocytes, or by genetically engineering cells from peripheral blood. The cells are activated and grown prior to transfusion into the recipient (tumour bearer).
context_page_description: Tumor-infiltrating lymphocytes are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of ‘tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells, in variable proportions. Their abundance varies with tumor type and stage and in some cases relates to disease prognosis
  TILs can often be found in the tumor stroma and within the tumor itself. Their functions can dynamically change throughout tumor progression and in response to anticancer therapy
  TILs are implicated in killing tumor cells. The presence of lymphocytes in tumors is often associated with better clinical outcomes.
context_section_description: In Adoptive T cell transfer therapy, TILs are expanded ex vivo from surgically resected tumors that have been cut into small fragments or from single cell suspensions isolated from the tumor fragments. Multiple individual cultures are established, grown separately and assayed for specific tumor recognition. TILs are expanded over the course of a few weeks with a high dose of IL-2 in 24-well plates. Selected TIL lines that presented best tumor reactivity are then further expanded in a "rapid expansion protocol" (REP), which uses anti-CD3 activation for a typical period of two weeks. The final post-REP TIL is infused back into the patient. The process can also involve a preliminary chemotherapy regimen to deplete endogenous lymphocytes in order to provide the adoptively transferred TILs with enough access to surround the tumor sites. This chemotherapy regimen is given 7 days before the expanded TIL infusion. This involves pretreatment with a combination of fludarabine and cyclophosphamide. Lympho-depletion is thought to eliminate the negative effects of other lymphocytes that may compete for growth factors and decrease anti-tumor effects of the TILs, depleting regulatory or inhibitory lymphocyte populations.
caption: Cancer specific T-cells can be obtained by fragmentation and isolation of tumor infiltrating lymphocytes, or by genetically engineering cells from peripheral blood. The cells are activated and grown prior to transfusion into the recipient (tumor bearer).
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