Article Figures & Data
Figures
- Figure 1.
Positive correlations between disease course and treatment-induced immune responses. A, the course of disease is shown above the timeline. Before radiotherapy and immunotherapy with TL-DC, the tumor rapidly progressed to regional lymph nodes (LN) and to the brain. After radiotherapy for brain metastases, the patient showed a prolonged time to progression of 16 months. Since December 2003, the patient has remained free of disease. Immunotherapeutic treatments are shown below the timeline. M3, MAGE-A3 peptide vaccination. Continuous vaccination with TL-DC correlated with long-term tumor control. B, antibody (Ab) responses against the cancer–testis antigens NY-ESO-1, MAGE-A1, and MAGE-A3. The patient developed NY-ESO-1 antibodies in November 2002 after gamma-knife radiation of brain metastasis. After surgical removal of mesenteric lymph node metastasis in December 2003, NY-ESO-1 antibody decreased and has not been detectable at all since July 2004. Antibody responses to MAGE-A1 and MAGE-A3 were not observed at any time. C, ex vivo tetramer analysis showing strong expansion of MAGE-A1p161–169–specific CD8+ T cells after radiotherapy and immunotherapy with TL-DC in 2004 that persisted throughout the course of immunotherapy and is still detectable ex vivo in the patient's peripheral blood without any evidence of detectable disease.
- Figure 2.
Induction of NY-ESO-1 antibody (Ab) after gamma-knife radiation. Changes in NY-ESO-1 antibody response were investigated by measuring serum immunoglobulin G (IgG) against recombinant full-length NY-ESO-1 protein and against 17 different synthetic 20 mer overlapping NY-ESO-1 peptides as antigens in standard ELISA. Before radiotherapy, the patient had not developed NY-ESO-1 antibodies. After gamma-knife radiation of brain metastasis, the patient sero-converted for NY-ESO-1 antibody. B-cell epitope mapping of NY-ESO-1 antibody response revealed that the presence of NY-ESO-1p31–50–specific antibody coincided with tumor cell destruction of brain metastasis. The presence of NY-ESO-1p161–180–specific antibody coincided with the development and subsequent surgical removal of mesenteric lymph node (LN) metastasis in December 2003. MRT images with coronal view on two of the brain metastases are shown before gamma-knife radiation (July 2002) and 2 months (October 2002) and 14 months (October 2003) after radiotherapy. Top images show the regression of the right occipital lesion, and bottom images show the transformation and subsequent regression of the right cerebellar lesion. OD, optical density.
- Figure 3.
Specificity, frequency, and effector function of CD8+ T-cell responses before and after radiotherapy/immunotherapy (RT/IT). A, IFN-γ secretion of CD8+ T cells following in vitro presensitization with peptides. Peptide-pulsed and unpulsed autologous monocyte-derived DC were used as antigen-presenting cells in ELISPOT. B, dominant MAGE-A1–specific CD8+ T-cell response after RT/IT detectable ex vivo by IFN-γ ELISPOT analysis. C, lytic activity of MAGE-A1–specific CD8+ T-cell clone NW1751–7/9 against MAGE-A1p161–169 peptide-pulsed autologous EBV-B cells and against the MAGE-A1/HLA-A1–expressing tumor cell line MZ2-MEL in chromium release assay at 10:1 effector/target ratio. MAGE-A3p168–176 peptide-pulsed autologous EBV-B cells, the MAGE-A1–negative tumor cell line NW-LC-1 (HLA-A1+) and K562 were used as negative controls and were not recognized. D, recognition of the vaccine by circulating CD4 and CD8 T cells is shown in ex vivo IFN-γ ELISPOT assay. Unpulsed DC were not recognized.
Additional Files
Supplementary Data
Files in this Data Supplement:
- Supplementary Methods - PDF file - 78K
- Supplementary Table 1 - XLSX file - 31K, Antigen expression of several melanoma metastases by RT-PCR.
Volume 2, Issue 5
