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 -