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

Mark E. Dudley, John R. Wunderlich, Thomas E. Shelton, Jos Even, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)332-342
Number of pages11
JournalJournal of Immunotherapy
Volume26
Issue number4
DOIs
StatePublished - Jul 2003
Externally publishedYes

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Tumor-Infiltrating Lymphocytes
Adoptive Transfer
Melanoma
Therapeutics
Neoplasms
T-Lymphocytes
HLA-A2 Antigen
Neoplasm Antigens
Interleukin-2
Lymphocytes
Biopsy

Keywords

  • Adoptive cell transfer
  • Immunotherapy
  • Melanoma
  • Tumor antigen
  • Tumor-infiltrating lymphocyte

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. / Dudley, Mark E.; Wunderlich, John R.; Shelton, Thomas E.; Even, Jos; Rosenberg, Steven A.

In: Journal of Immunotherapy, Vol. 26, No. 4, 07.2003, p. 332-342.

Research output: Contribution to journalArticle

Dudley, Mark E. ; Wunderlich, John R. ; Shelton, Thomas E. ; Even, Jos ; Rosenberg, Steven A. / Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. In: Journal of Immunotherapy. 2003 ; Vol. 26, No. 4. pp. 332-342.
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