Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients.

  • Dudley M
  • Wunderlich J
  • Shelton T
 et al. 
  • 186


    Mendeley users who have this article in their library.
  • 333


    Citations of this article.


The generation of T lymphocytes with specific reactivity against tumor antigens is a prerequisite for effective adoptive transfer therapies. Melanoma-specific lymphocyte cultures can be established from tumor infiltrating lymphocytes (TILs) by in vitro culture in high levels of IL-2. We have optimized methods for generating melanoma-reactive TIL cultures from small resected tumor specimens. We report a retrospective analysis of 860 attempted TIL cultures from 90 sequential melanoma biopsy specimens from 62 HLA-A2+ patients. Multiple independent TIL derived from a single tumor often exhibited substantial functional and phenotypic variation. Tumor specific activity was detected in TIL from 29 (81%) of 36 patients screened. TIL cultures selected for high activity were generally capable of large numerical expansion using a single round of a rapid expansion protocol. Limited clonal T-cell populations in an oligoclonal TIL culture could confer specific tumor recognition in these highly selected, highly expanded TIL cultures. These methods were efficient at generating TILs suitable for adoptive transfer therapy.

Author-supplied keywords

  • Antigens
  • Antigens: chemistry
  • CD4-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes: immunology
  • CD8-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes: immunology
  • Cell Separation
  • Cytokines
  • Cytokines: metabolism
  • Flow Cytometry
  • HLA-A2 Antigen
  • HLA-A2 Antigen: metabolism
  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive
  • Immunotherapy, Adoptive: methods
  • Immunotherapy: methods
  • Interleukin-2
  • Interleukin-2: biosynthesis
  • Interleukin-2: metabolism
  • Leukocytes, Mononuclear
  • Leukocytes, Mononuclear: metabolism
  • Lymphocytes, Tumor-Infiltrating
  • Lymphocytes, Tumor-Infiltrating: metabolism
  • Melanoma
  • Melanoma: immunology
  • Melanoma: metabolism
  • Melanoma: therapy
  • Phenotype
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell: metabolism

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Mark E Dudley

  • John R Wunderlich

  • Thomas E Shelton

  • Jos Even

  • Steven A Rosenberg

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free