title: Value of large scale expansion of tumor infiltrating lymphocytes in a compartmentalised gas-permeable bag: interests for adoptive immunotherapy.
abstract: BACKGROUND
  Adoptive cell therapy (ACT) has emerged as an effective treatment for patients with metastatic melanoma. However, there are several logistical and safety concerns associated with large-scale ex vivo expansion of tumour-specific T lymphocytes for widespread availability of ACT for cancer patients. To address these problems we developed a specific compartmentalised bag allowing efficient expansion of tumour-specific T lymphocytes in an easy handling, closed system.
  
  
  METHODS
  Starting from lymph nodes from eight melanoma patients, we performed a side-by-side comparison of Tumour-Infiltrating Lymphocytes (TIL) produced after expansion in the compartmentalised bag versus TIL produced using the standard process in plates. Proliferation yield, viability, phenotype and IFNγ secretion were comparatively studied.
  
  
  RESULTS
  We found no differences in proliferation yield and cell viability between both TIL production systems. Moreover, each of the cell products complied with our defined release criteria before being administered to the patient. The phenotype analysis indicated that the compartmentalised bag favours the expansion of CD8+ cells. Finally, we found that TIL stimulated in bags were enriched in reactive CD8+ T cells when co-cultured with the autologous melanoma cell line.
  
  
  CONCLUSIONS
  The stimulation of TIL with feeder cells in the specifically designed compartmentalised bag can advantageously replace the conventional protocol using plates. In particular, the higher expansion rate of reactive CD8+ T cells could have a significant impact for ACT.
authors.affiliation: Cell and Gene Therapy Unit (UTCG): CIC biotherapy INSERM 0503 Hôtel-Dieu University Hospital 44093 Nantes cedex 01 France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zuliani
authors.forename: Julien
authors.initials: J
authors.lastname: David
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bercegeay
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Pandolfino
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rodde-Astier
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.forename: Cécile
authors.initials: C
authors.lastname: Coissac
authors.forename: Bruno
authors.initials: B
authors.lastname: Delorme
authors.forename: Soraya
authors.initials: S
authors.lastname: Saïagh
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D005740:Gases / Q000378:metabolism*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D010539:Permeability
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D005740:Gases; D007371:Interferon-gamma