scholarly journals Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests

2006 ◽  
Vol 17 (6) ◽  
pp. 974-980 ◽  
Author(s):  
W.J. Lesterhuis ◽  
I.J.M. de Vries ◽  
D.H. Schuurhuis ◽  
A.C.I. Boullart ◽  
J.F.M. Jacobs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dendritic Cells ◽  
T Cell ◽  
Cancer Patients ◽  
T Cell Responses ◽  
Skin Tests ◽  
Cell Responses ◽  
Colorectal Cancer Patients

scholarly journals Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients

2013 ◽  
Vol 62 (8) ◽  
pp. 1293-1301 ◽  
Author(s):  
Michael A. Morse ◽  
Arvind Chaudhry ◽  
Elizabeth S. Gabitzsch ◽  
Amy C. Hobeika ◽  
Takuya Osada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
Neutralizing Antibodies ◽  
Adenoviral Vector ◽  
T Cell Responses ◽  
Cell Responses ◽  
Colorectal Cancer Patients

A vaccinia-based vaccine (TroVax) targeting the oncofetal antigen 5T4 administered before and after surgical resection of colorectal cancer liver metastases: Phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2574-2574 ◽  
Author(s):  
A. Dangoor ◽  
D. Burt ◽  
R. Harrop ◽  
N. Drury ◽  
C. Hamer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Immune Responses ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Colorectal Liver Metastases ◽  
T Cell Responses ◽  
Cell Responses ◽  
T Cell Infiltration ◽  
Colorectal Cancer Patients

2574 Background: Oncofetal antigen 5T4 is expressed by most colorectal cancers. Administration of a vaccine combining a Modified Vaccinia Ankara (MVA) vector with 5T4 elicits immune responses in late-stage colorectal cancer patients. This trial seeks to investigate the immunological effects of the vaccine both in peripheral blood and locally in tumour tissue resected during potentially curative surgery for colorectal liver metastases. Some patients may have micrometastatic disease, a potential target for immunotherapy. Methods: Colorectal cancer patients selected for resection of liver metastases were eligible. Recruitment of up to 20 patients was planned. Following screening they received 2 vaccinations prior to, and 2 after, surgery. Primary endpoint was assessment of the immune response at time of surgery. Blood was taken for analysis at screening and 2 weeks after each vaccination. A tumour biopsy was obtained at surgery. T-cell responses were assessed using proliferation and gamma-interferon ELISPOT assays; ELISA used to assess serological response. Immunohistochemical analysis was used to confirm tumour antigen expression and the nature of T-cell infiltration into the liver. If 5T4-specific immune responses were demonstrated patients were offered further vaccinations at 20 and 28 weeks post surgery. Results: Of 20 patients recruited, 16 were eligible for assessment, 4 excluded, 1 due to hepatocellular carcinoma, 3 with inoperable disease. There was no grade III/IV toxicity related to vaccination. Tumour expression of 5T4 was confirmed in all cases, local T-cell infiltration consisted predominantly of CD4 cells. According to proliferation assays, 8 of 16 patients had T-cell responses at time of surgery and 12 of 16 in total to date. 14 patients have developed 5T4-specific antibody responses. At median follow up of 8.4 months 7 of 16 patients have disease recurrence. Conclusions: The MVA-5T4 vaccine (TroVax) was safe and well tolerated in all patients undergoing resection of colorectal liver metastases. 5T4 specific cellular and/or humoral immune responses were induced in the majority of patients following vaccination with TroVax. [Table: see text]

T Cell Responses in Patients Vaccinated with Telomerase (hTERT)-mRNA Transfected Dendritic Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 373-373
Author(s):  
Else Marit Inderberg Suso ◽  
Anne-Marie Rasmussen ◽  
Steinar Aamdal ◽  
Svein Dueland ◽  
Gustav Gaudernack ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Stable Disease ◽  
T Cell Responses ◽  
Htert Mrna ◽  
Cell Responses

Abstract Abstract 373 Two cancer patients were vaccinated with dendritic cells (DC) loaded with telomerase (hTERT) mRNA to investigate the safety, tolerability and immunological response to vaccination prior to the start of a new phase I/II clinical trial. Following written informed consent one primary lung adenocarcinoma with metastasis and one patient with a relapsed pancreatic ductal type of adenocarcinoma, were treated with autologus monocyte-derived DC transfected with mRNA encoding hTERT. The patients first received four weekly injections administered intradermally followed by monthly booster injections. Peripheral blood mononuclear cells (PBMC) at each vaccination time point were tested in vitro with transfected DC and a panel of 24 overlapping hTERT peptides. In addition, hTERT-specific CD8+ T cells were monitored by pentamer staining. The treatment was well tolerated with minor side effects. Immune responses against telomerase-transfected DC and some of the overlapping hTERT peptides were detected in both patients. We also detected hTERT-specific CD8+ T cells in both patients by pentamer staining in post-vaccination samples. The lung cancer patients obtained a stable disease that lasted 18 months while the patient with pancreas cancer who started the DC vaccination in July 2007 following palliative chemotherapy, still is in stable disease by continuously boost vaccination. T-cell responses against telomerase epitopes have also been identified in both non-vaccinated cancer patients and cancer patients previously vaccinated with telomerase peptide. Since patients with these findings often show extraordinary clinical courses of their disease we hypothesize that it exists a high degree of immunogenicity and HLA promiscuity for some telomerase epitopes. In this study we have shown that vaccination with hTERT-mRNA transfected DC is safe and able to induce robust immune responses to several telomerase T-cell epitopes both in CD4+ and CD8+ T cells. This opens up the possibility for a broad clinical application of mRNA hTERT DC vaccines. Furthermore, responding T cells identified in these patients are strong candidates for T-cell receptor cloning and the receptors identified can thereafter be transferred into T cells creating the next generation of immuno-gene therapy with retargeted T cells. Disclosures: No relevant conflicts of interest to declare.

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