Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709)
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Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709). / Køllgaard, Tania; Duval, Lone; Schmidt, Henrik; Kaltoft, Keld; Seremet, Tina; Andersen, Mads Hald; Maase, Hans von der; Straten, Per thor; Hadrup, Sine R.
I: Cytotherapy, Bind 11, Nr. 5, 2009, s. 631-41.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709)
AU - Køllgaard, Tania
AU - Duval, Lone
AU - Schmidt, Henrik
AU - Kaltoft, Keld
AU - Seremet, Tina
AU - Andersen, Mads Hald
AU - Maase, Hans von der
AU - Straten, Per thor
AU - Hadrup, Sine R
N1 - Keywords: Adult; Antigens, Neoplasm; Biopsy; CD8-Positive T-Lymphocytes; Cell Line; Clone Cells; Drug Administration Routes; Flow Cytometry; HLA Antigens; Humans; Immunotherapy, Adoptive; Injections; Longitudinal Studies; Middle Aged; Monitoring, Immunologic; Neoplasm Metastasis; Neoplasm Proteins; Receptors, Antigen, T-Cell; Staining and Labeling; Transduction, Genetic
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1080/14653240902923146
DO - 10.1080/14653240902923146
M3 - Journal article
C2 - 19530030
VL - 11
SP - 631
EP - 641
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 5
ER -
ID: 20568741