Preliminary results of a phase II-study: Vaccination therapy of pancreatic carcinoma patients with autologous, tumor lysate pulsed dendritic cells

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14102-14102
Author(s):  
C. Bauer ◽  
M. Dauer ◽  
M. Schnurr ◽  
J. Junkmann ◽  
F. Bauernfeind ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Pancreatic Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Local Disease ◽  
Vaccination Therapy

14102 Background: Vaccination trials in the experimental and in the clinical setting have shown that it is possible to use dendritic cells (DC) to induce a specific antitumoral immune response. In this study, a protocol for the treatment of patients with metastasised pancreatic carcinoma with autologous, tumor-lysate pulsed dendritic cells was established. Methods: Patients with strong suspicion of pancreatic carcinoma receiving abdominal surgery are recruited to the study. Tumor-lysate is derived by freeze-taw-cycles from surgically derived tissue specimens. After recurrence of histologically verified pancreatic carcinoma or in a primarily palliative situation, patients are eligible for DC vaccination. DC are derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-alpha and PgE2. DC are applicated intracutaneously into the groin region three times in twice weekly cycles, then in monthly cycles. Immune response is controlled by DTH skin testing. Samples of non adherent cells are frozen for future MLR and ELISPOT assays. Main study end point is partial or complete remission four months after the start of vaccination. Alternative end points are adverse effects, quality of life, one-year survival and immuno-monitoring. Results: Tumor material of 49 patients has been worked up to tumor lysate and stored for future vaccinations. Four patients have received dendritic cell vaccination. Two of these patients have received their four months staging CT. In one case local disease was stable. The other patient showed progressive disease. A more pronounced proliferation of specific T cells compared to the control setting could be demonstrated by MLR assay. Discussion: A protocol for vaccination with tumor lysate pulsed dendritic cells of patients with pancreatic carcinoma has been established. Four patients have been vaccinated with dendritic cells according to a phase II study protocol. Vaccination was tolerated well. Because of a severe adverse reaction after the beginning of gemcitabine therapy, vaccination had to be omitted intercurrently with this patient. Results of most immuno monitoring assays are pending. One patient receiving DC vaccination therapy showed stable local disease. No significant financial relationships to disclose.

Immunological and clinical response after vaccination therapy of pancreatic carcinoma patients with autologous, tumor-lysate pulsed dendritic cells: Results of a phase II-study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4579-4579 ◽  
Author(s):  
C. Bauer ◽  
M. Dauer ◽  
S. Saraj ◽  
M. Schnurr ◽  
K. Jauch ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Pancreatic Carcinoma ◽  
Phase Ii Study ◽  
Immunological Response ◽  
Autologous Tumor ◽  
Adherent Cells ◽  
Tumor Lysate ◽  
Advanced Pancreatic Carcinoma ◽  
Vaccination Therapy

4579 Background: Multiple studies in the experimental and in the clinical setting have shown that vaccine therapy using dendritic cells can induce antitumor immunity. Here, we report about the results of a phase II-study using autologous, tumor-lysate pulsed dendritic cells for the treatment of patients with advanced pancreatic carcinoma. Methods: Pancreatic carcinoma patients receiving abdominal surgery were included into to the study protocol. Tumor-lysate was derived by freeze-taw-cycles from surgically derived tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-a and PgE2. DC were applicated intracutaneously into the groin region every other week for three cycles, then monthly. All patients received standard chemotherapy with gemcitabine concomitantly. Immune response was controlled by DTH skin testing. Samples of non adherent cells were frozen for MLR and ELISPOT assays to monitor immune response ex vivo. Main study end point was partial or complete remission. Results: Ten patients have received dendritic cell vaccination so far. Of these, one patient developed a partial remission after a four-months course of vaccination therapy. Another patient showed stable disease after having received five vaccinations. Both patients showed immunological response. The patient with stable disease had a mean of 56 IFN-γ positive spots per 50E3 DC-stimulated non adherent cells prior to vaccination. After vaccination, this number increased to 191 spots per 50E3 cells (negative control: 5; positive control: 315). Both patients are alive 13 and 7 months after the start of vaccination therapy, respectively. Conclusions: Vaccination therapy with dendritic cells can be of clinical benefit in the setting of advanced pancreatic carcinoma. Clinical responses were associated with the induction of a stable immunological response. No significant financial relationships to disclose.

Autologous tumor lysate-pulsed dendritic cell vaccination therapy after resection of stage IIA (T2N0, T3N0) esophageal cancer: An analysis of immunological responses.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 96-96
Author(s):  
Yasuyoshi Sato ◽  
Koichi Yagi ◽  
Kazuhiko Mori ◽  
Hirokazu Matsushita ◽  
Kazuhiro Kakimi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Dendritic Cell ◽  
Immune Responses ◽  
R0 Resection ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Binding Prediction ◽  
Dc Vaccines ◽  
Vaccination Therapy

96 Background: Immunotherapy using active immunization of tumor associated antigens has been expected to improve the prognosis of malignant tumor patients. We conducted phase I trial to investigate safety and efficacy of autologous tumor lysate-pulsed dendritic cell (DC) vaccination therapy after resection for esophageal cancer. We already reported the clinical results for enrolled 11 patients. All patients completed the protocol therapy and no treatment-related adverse events more than grade 3 was observed (primary endpoint), and recurrence rate within 2 years was 18% (n = 2). In this study, we further analyzed the immune responses in vaccinated patients. Methods: Patients with stage IIA (T2N0 or T3N0, UICC TNM classification 6th edition) esophageal cancer after curative (R0) resection were eligible. Tumor lysate we used for DC vaccines potentially contains mutated proteins (neoantigens) derived from somatic mutations. Patients received DC vaccines (more than 5.0×106 cells) 6 times every 2 weeks. We evaluated neutrophil-to-lymphocyte ratio (NLR) in each patient from CRF data. We identified candidate neoantigens by next generation sequencing and MHC class I binding prediction algorism. We screened the immune responses against those neoantigens using HLA transgenic mice and healthy human PBMCs. Results: Absolute lymphocyte counts, absolute neutrophil counts and NLR were not specifically different between patients with or without recurrence. For specific immune responses, we observed the reactivity in 6 out of 59 candidate neoepitopes identified from two patients in HLA transgenic mouse system. Two out of 6 peptides displayed reactivity in human healthy PBMCs. Conclusions: We analyzed immune responses to predicted candidate neoantigens. We are now investigating immune landscape in the tumor using RNA sequencing data and its relevance to the antigen responses. Clinical trial information: UMIN000002837.

scholarly journals A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma

Hepatology ◽  
2008 ◽  
Vol 49 (1) ◽  
pp. 124-132 ◽  
Author(s):  
Daniel H. Palmer ◽  
Rachel S. Midgley ◽  
Noweeda Mirza ◽  
Elizabeth E. Torr ◽  
Forhad Ahmed ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dendritic Cells ◽  
Phase Ii ◽  
Adoptive Immunotherapy ◽  
Phase Ii Study ◽  
Tumor Lysate

scholarly journals CTIM-18. DENDRITIC CELL VACCINATION IN CONJUNCTION WITH ADJUVANT TLR-3 AGONIST ADMINISTRATION ENHANCES PRO-INFLAMMATORY IMMUNE RESPONSES AND IS ASSOCIATED WITH EXTENDED SURVIVAL IN MALIGNANT GLIOMA PATIENTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii36-ii37
Author(s):  
Carolina Chavez ◽  
Richard Everson ◽  
Joey Orpilla ◽  
Alexander Lee ◽  
Sara Khattab ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Malignant Glioma ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Who Grade ◽  
Pulsed Dc ◽  
Extended Survival

Abstract Despite recent advances with immunotherapy in other tumor types, malignant glioma patients have not shown a therapeutic benefit, potentially due to the insufficient activation of an immune response. We and others have documented immune responses and extended survival following dendritic cell (DC) vaccination in small clinical trials. In this Phase II clinical trial, we randomized malignant glioma patients to receive autologous tumor lysate pulsed DC vaccination with and without adjuvant toll-like receptor (TLR) agonists. Treatment with TLRs in cancer patients has been shown to activate the innate immune response by inducing the expression of pro-inflammatory factors and cytokines. Twenty-three patients with WHO grade III or IV glioma received three intradermal injections of autologous tumor lysate-pulsed DC on days 0, 14, and 28 in conjunction with either a placebo adjuvant, TLR-7 agonist (Resiquimod), or TLR-3 agonist (Poly ICLC). We observed a difference in survival for the DC-vaccinated patients who received adjuvant Poly ICLC treatment of 54 months over adjuvant placebo (20 months) and adjuvant Resiquimod (28 months) groups (P = 0.04). The patient cohorts were balanced for WHO grade, IDH mutation, and MGMT methylation status. Mass cytometry (CyTOF) analysis of patient peripheral blood mononuclear cells (PBMCs) showed increased levels of the monocyte populations CD14+CD16- and CD14dimCD16+ after Poly ICLC treatment. In addition, gene expression analysis of the PBMC populations using single cell RNA sequencing demonstrated increased expression of pro-inflammatory genes after adjuvant Poly ICLC and Resiquimod treatment. Nonetheless, a greater fold change increase and a larger pro-inflammatory repertoire was observed in the Poly ICLC group. Overall, these findings demonstrate that adjuvant Poly ICLC increases the number of circulating monocytes and induces a large pro-inflammatory response, which may account for the survival differences observed over adjuvant Resiquimod and placebo.

scholarly journals Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells

2000 ◽  
pp. 300-306 ◽  
Author(s):  
M Schott ◽  
J Feldkamp ◽  
D Schattenberg ◽  
T Krueger ◽  
C Dotzenrath ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Parathyroid Carcinoma ◽  
Interleukin 4 ◽  
Delayed Type Hypersensitivity ◽  
Dendritic Cell Vaccination ◽  
Tumor Lysate

BACKGROUND: Cytotoxic T-lymphocyte-mediated tumor immunity against major histocompatibility antigen class II-negative tumors requires help from CD4(+) T-cells. The major antigen presenting cells for CD4(+) cell activation are dendritic cells. Studies in mice and humans have demonstrated the potent capacity of these cells to induce specific antitumor immunity. OBJECTIVE: To control the growth of a metastasized parathyroid carcinoma, by immunizing a patient with tumor lysate and parathyroid hormone-pulsed dendritic cells. DESIGN AND METHODS: Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor alpha. Antigen-loaded dendritic cells were delivered by subcutaneous and intralymphatical injections. After five cycles, we added keyhole limpet hemocyanin (KLH) as a CD4(+) helper antigen. RESULTS: After 10 vaccinations, a specific cellular immune response to tumor lysate was observed. In vitro T-cell proliferation assays revealed a dose-dependent stimulation index of 1.8-5.7 compared with 0.9-1.1 before vaccination. In vivo immune response was demonstrated by positive delayed-type hypersensitivity toward tumor lysate. Intradermal injection of tumor lysate resulted in an erythema and induration, suggesting the efficient generation of tumor lysate-specific memory T-cells. CONCLUSIONS: These data indicate that dendritic cell vaccination can induce in vitro and in vivo responses in a highly malignant endocrine carcinoma. Regardless of the clinical outcome of our patient, this approach might be generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies, such as adrenal carcinomas and metastasized medullary and anaplastic thyroid carcinomas.

Sign in / Sign up

Export Citation Format

Share Document