title: Preclinical evaluation of adoptive cell therapy for patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Interleukin-2 (IL-2) shows encouraging clinical results in metastatic renal cell carcinoma (RCC) patients, but is limited by substantial toxicity. Cell-based therapy holds a promise, but past attempts in RCC were unsuccessful. Advances in tumor-infiltrating lymphocytes (TIL) generation technology and modified clinical protocols recently yielded a 50% response in refractory melanoma patients.
  
  
  METHODS
  RCC-derived TIL and tumor cells were processed by current protocols from tumor specimens in a clean laboratory. The expanded TIL were characterized and tested in functional assays.
  
  
  RESULTS
  The TIL cultures were efficiently generated and massively expanded. Virtually all the expanded cells were T-cells, but a considerable variability in the CD4/CD8 ratio and a frequent CD4-CD8-phenotype were observed. The TIL exerted cytotoxic or IFNgamma-release activities against autologous targets in major histocompatibility (MHC) class I-restricted and -independent functional patterns. The functional results were superior to former technologies.
  
  
  CONCLUSIONS
  Recent developments in TIL generation technology and clinical patient conditioning protocols indicate that the TIL-based approach for RCC could be revisited.
authors.affiliation: Ella Institute of Melanoma, Sheba Cancer Research Center, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Tali
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authors.lastname: Cohen-Sinai
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Besser
authors.forename: Kfir
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authors.lastname: Oved
authors.forename: Orit
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authors.lastname: Itzhaki
authors.forename: Rachel
authors.initials: R
authors.lastname: Seidman
authors.forename: Eduard
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authors.lastname: Fridman
authors.forename: Avraham J
authors.initials: AJ
authors.lastname: Treves
authors.forename: Yona
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authors.lastname: Keisari
authors.forename: Zohar
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authors.lastname: Dotan
authors.forename: Jacob
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authors.lastname: Ramon
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter