Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709).
OBJECTIVE
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.
Køllgaard
Tania
T
Center for Cancer Immune Therapy (CCIT), University Hospital Herlev, Herlev, Denmark.
Duval
Lone
L
Schmidt
Henrik
H
Kaltoft
Keld
K
Seremet
Tina
T
Andersen
Mads Hald
MH
Maase
Hans von der
Hv
Straten
Per thor
Pt
Hadrup
Sine R
SR
D000328:Adult; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D004333:Drug Administration Routes; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007267:Injections; D008137:Longitudinal Studies; D058965:MART-1 Antigen; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000008:administration & dosage*; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage*; D013194:Staining and Labeling; D014161:Transduction, Genetic
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell