Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709)

Tania Køllgaard, Lone Duval, Henrik Schmidt, Keld Kaltoft, Tina Seremet, Mads Hald Andersen, Hans von der Maase, Per thor Straten, Sine Reker Hadrup

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background aims Adoptive transfer of tumor-specific lymphocytes is a promising strategy in the treatment of cancer. We conducted intratumoral administration of an allogeneic irradiated continuous T-cell line (C-Cure 709) expressing an HLA-A2-restricted MART-1-specific T-cell receptor (TCR) into HLA-A2+ melanoma patients. The C-Cure 709 cell line is cytotoxic against MART-1+ HLA-A2+ melanoma cell lines and secretes several immune stimulatory cytokines upon stimulation. Methods Anti-tumor immune responses against the commonly expressed tumor antigen (Ag) MART-1 were longitudinally analyzed in peripheral blood by fluorescence-activated cell sorting (FACS) before and after intratumoral injection of C-Cure 709. Results No treatment-induced increase in Ag-specific T-cell frequencies was observed in peripheral blood, and the phenotype of MART-1-specific T cells was very stable during the treatment. Interestingly, despite a very stable frequency of MART-1-specific T cells over the course of treatment, clonotype mapping revealed that the response was in fact highly diverse and dynamic, with new clonotypes emerging during treatment. Only a few clonotypes were recurrently detected in consecutive samples. One MART-1-specific T-cell clone disappearing from peripheral blood was later detected in a metastatic lesion. Conclusions Sequence analyzes of the CDR3 region revealed conserved structural characteristics in the MART-1-specific TCR used by T-cell clones.
Original languageEnglish
JournalCytotherapy
Volume11
Issue number5
Pages (from-to)631-641
Number of pages11
ISSN1465-3249
DOIs
Publication statusPublished - 2009
Externally publishedYes

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