Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a Hapten-modified autologous tumor vaccine

Marialuisa Sensi, Cinthia Farina, Cristina Maccalli, Raffaella Lupetti, Gabriella Nicolini, Andrea Anichini, Giorgio Parmiani, David Berd

Research output: Contribution to journalArticle

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Abstract

Metastatic melanoma patients treated with an autologous DNP-modified tumor cell vaccine develop inflammatory responses in metastatic tumors characterized by infiltration of CD8+ T cells. To further define this immune response, we analyzed T cell receptor β-chain variable (TCRBV) region repertoire in biopsy specimens and peripheral blood lymphocytes of six patients. After administration of DNP vaccine, a restricted set of TCRBV gene families was found to be expanded compared with prevaccine metastases. In several postvaccine lesions of one patient, obtained over a 2-yr period, TCRBV14+ T cells were clonally expanded and identical T cell clonotypes could be detected. Two major recurring clones were biased toward the use of TCRBJ1S5. Furthermore, T cell lines derived from two such infiltrated skin lesions and, enriched in TCRBV14+ T cells, displayed HLA-class I-restricted lysis of the autologous melanoma cells. Clonal expansion of T cells was demonstrated in the T cell-infiltrated, postvaccine metastasis of a second patient as well. These results indicate that vaccination with autologous, DNP-modified melanoma cells can expand selected clones of T cells at the tumor site and that such clones are potentially destructive to the tumor.

Original languageEnglish
Pages (from-to)710-717
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number4
Publication statusPublished - 15 Feb 1997
Externally publishedYes

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Cancer Vaccines
Haptens
Melanoma
Neoplasm Metastasis
T-Lymphocytes
Clone Cells
Therapeutics
Neoplasms
T-Cell Antigen Receptor
Vaccination
Vaccines
Lymphocytes
Biopsy
Cell Line
Skin

Keywords

  • cytotoxic T cells
  • melanoma
  • T cell receptor
  • tumor-infiltrating lymphocytes
  • vaccine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a Hapten-modified autologous tumor vaccine. / Sensi, Marialuisa; Farina, Cinthia; Maccalli, Cristina; Lupetti, Raffaella; Nicolini, Gabriella; Anichini, Andrea; Parmiani, Giorgio; Berd, David.

In: Journal of Clinical Investigation, Vol. 99, No. 4, 15.02.1997, p. 710-717.

Research output: Contribution to journalArticle

Sensi, M, Farina, C, Maccalli, C, Lupetti, R, Nicolini, G, Anichini, A, Parmiani, G & Berd, D 1997, 'Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a Hapten-modified autologous tumor vaccine', Journal of Clinical Investigation, vol. 99, no. 4, pp. 710-717.
Sensi, Marialuisa ; Farina, Cinthia ; Maccalli, Cristina ; Lupetti, Raffaella ; Nicolini, Gabriella ; Anichini, Andrea ; Parmiani, Giorgio ; Berd, David. / Clonal expansion of T lymphocytes in human melanoma metastases after treatment with a Hapten-modified autologous tumor vaccine. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 4. pp. 710-717.
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