Pure autologous tumor cells (TC) and dendritic cells (DC) with GM-CSF: Patient-specific vaccine for metastatic melanoma

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 7547-7547
Author(s):  
R. O. Dillman ◽  
S. R. Selvan ◽  
P. M. Schiltz ◽  
K. Allen ◽  
C. Depriest ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Gm Csf

Patient-specific vaccines derived from proliferating autologous tumor cell lines and dendritic cells: Results of a phase II trial in metastatic melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8555-8555
Author(s):  
R. O. Dillman ◽  
S. R. Selvan ◽  
P. M. Schiltz ◽  
C. DePriest ◽  
C. Peterson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Delayed Type Hypersensitivity ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Gm Csf ◽  
Measurable Disease

8555 Background: Patient-specific vaccines utilizing proliferating tumor cells, or tumor stem cells, may be the ideal products for active specific immunotherapy. Methods: Eligible patients had recurrent or metastatic melanoma from which a cell line was established, expanded to 200 million cells, incubated with interferon-gamma, irradiated and cryopreserved. Autologous dendritic cells (DC) were derived from peripheral blood mononuclear cells cultured in IL-4 and GM-CSF. DC were incubated with the irradiated tumor cells, then cryopreserved in 20- million-cell aliquots, which were thawed, washed and suspended in 500 micrograms of GM-CSF for injection. Treatment consisted of s.c. injections weekly × 3, then monthly × 5 in a 2-stage phase II trial with two stratifications. Patients were characterized as having objectively measurable disease (OMD) or non-measurable disease (NMD). Plans were to enroll 30 to 80 patients: 15 to 40 with OMD, 15 to 40 with MD. Objectives were to determine safety, frequency of conversion of delayed type hypersensitivity (DTH) reactions to irradiated autologous tumor cells, objective response rate (ORR) using RECIST criteria, progression-free survival (PFS), overall survival (OS), and comparison to a historical control group. Results: Between January 2001 and April 2006, 55 patients were enrolled; 53 were eligible and evaluable. The 30 men and 23 women had a median age of 50 years; 15 had OMD and 38 NMD. Patients received an average of 7.4 vaccinations out of a possible 8. Treatment was well- tolerated. 25% had a positive tumor DTH test: 1 at baseline, 7 after 3 injections, 5 after 8 injections. ORR was 0/15. Follow up for the 39 surviving patients ranges from 7 to 67 months with a median of 30 months. Median PFS is 7.1 months with 24 patients remaining progression-free. Only 14 patients have died; median OS has not been reached. 5-year projected survival is 70%; 20 patients are alive 2.5 to 5.5 years from start of vaccine. OS is better than observed for 48 comparable patients that we treated previously in a trial with irradiated tumor cells without DC (p=0.016). Conclusion: This patient-specific vaccine approach is feasible, safe, associated with encouraging survival, and warrants further investigation. No significant financial relationships to disclose.

Pure autologous tumor cells (TC) and dendritic cells (DC) with GM-CSF: Patient-specific vaccine for metastatic melanoma

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 7547-7547
Author(s):  
R. O. Dillman ◽  
S. R. Selvan ◽  
P. M. Schiltz ◽  
K. Allen ◽  
C. Depriest ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Gm Csf

Phase I/II Trial of Melanoma Patient–Specific Vaccine of Proliferating Autologous Tumor Cells, Dendritic Cells, and GM-CSF: Planned Interim Analysis

2004 ◽  
Vol 19 (5) ◽  
pp. 658-665 ◽  
Author(s):  
Robert Dillman ◽  
Senthamil Selvan ◽  
Patric Schiltz ◽  
Cheryl Peterson ◽  
Kanoe Allen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Phase I ◽  
Tumor Cells ◽  
Melanoma Patient ◽  
Interim Analysis ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Gm Csf

Phase I/II Trial of Melanoma Patient–Specific Vaccine of Proliferating Autologous Tumor Cells, Dendritic Cells, and GM-CSF: Planned Interim Analysis

2004 ◽  
Vol 19 (5) ◽  
pp. 658-665 ◽  
Author(s):  
Robert Dillman ◽  
Senthamil Selvan ◽  
Patric Schiltz ◽  
Cheryl Peterson ◽  
Kanoe Allen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Phase I ◽  
Tumor Cells ◽  
Melanoma Patient ◽  
Interim Analysis ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Gm Csf

Survival by stage and tumor measurability in metastatic melanoma patients treated with autologous dendritic cell tumor cell vaccines.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2637-2637
Author(s):  
Robert O. Dillman ◽  
Andrew N Cornforth ◽  
Edward Francis McClay ◽  
Carol DePriest
Keyword(s):  
Dendritic Cells ◽  
Tumor Cell ◽  
Metastatic Melanoma ◽  
Tumor Cell Line ◽  
Patient Specific ◽  
Autologous Tumor Cell ◽  
Autologous Tumor ◽  
Phase Ii Trials ◽  
Stage 4 ◽  
Melanoma Patients

2637 Background: Survival of cancer patients is greatly affected by stage and tumor burden. The purpose of this study was to determine survival for melanoma patients who were treated with patient specific vaccines in the context of prospective clinical trials, by cohorts defined by stage and tumor measurability. Methods: Metastatic melanoma patients were treated with autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines (DCV). All patients had a metastatic melanoma lesion surgically resected, from which a tumor cell line was established. Irradiated tumor cells (ITC) were incubated with autologous dendritic cells (DC) to produce the DCV, which were injected s.c. in 500 micrograms GM-CSF weekly x 3 weeks, then monthly for 5 months. Data was pooled for DCV-treated patients enrolled in either of two phase II trials: one single-arm (NCT00948480), one randomized (NCT00436930). Patients were assigned to one of three cohorts based on their most advanced stage of disease prior to treatment, and whether they had measurable disease at the time of treatment. Survival was determined per Kaplan and Meier. Results: The final therapeutic products consisted of autologous DC with non-phagocytosed ITC making up 0% to 20% of cells in the final product. There were 45 men and 27 women. Median age was 52 years (range 17 to 83). Tumor sources were 37-lymph node, 20-viscera, and 15-soft tissue. No patients were lost to follow up; all surviving patients were followed 5 years. Toxicity was minimal. Median overall survival (OS) for all 72 patients was 49.4 mos; 5-year OS 46%. There was no correlation between survival and the number of DC or ITC in the first three injections. Patients with recurrent stage 3 disease that had not recurred (n=18) had a 72% 5-year OS; patients with non-measurable stage 4 (n=30) had a 53% 5-year OS. Patients with measurable stage 4 (n=18) had received an average of four prior therapies. They had a median OS of 18.5 months, and 2-year OS of 46%. Conclusions: This patient-specific DCV was associated with encouraging survival in all three clinical subsets. Because of its mechanism of action and absence of toxicity, it should be evaluated further. Clinical trial information: NCT00948480, NCT00436930.

Immunogenicity, Including Vitiligo, and Feasibility of Vaccination With AutologousGM-CSF–Transduced Tumor Cells in Metastatic Melanoma Patients

2005 ◽  
Vol 23 (35) ◽  
pp. 8978-8991 ◽  
Author(s):  
Rosalie M. Luiten ◽  
Esther W.M. Kueter ◽  
Wolter Mooi ◽  
Maarten P.W. Gallee ◽  
Elaine M. Rankin ◽  
...  
Keyword(s):  
T Cells ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
High Dose ◽  
Autologous Tumor ◽  
Free Survival ◽  
Gm Csf ◽  
Melanoma Patients ◽  
Disease Free

PurposeTo determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients.Patients and MethodsSixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays.ResultsThe high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1– or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1– and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-γ on specific antigenic stimulation.ConclusionWe conclude that vaccination with GM-CSF–transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.

Patient-specific immunotherapy utilizing putative tumor stem cells in patients with metastatic melanoma: A pooled analysis comparing tumor cell and dendritic cell vaccines in two phase II trials and a randomized phase II trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2569-2569
Author(s):  
Robert Owen Dillman ◽  
Carol DePriest ◽  
Cristina de Leon ◽  
Neil M. Barth ◽  
Edward Francis McClay ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Pooled Analysis ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Tumor Stem Cells ◽  
Phase Ii Trials ◽  
Randomized Phase Ii

2569 Background: Metastatic melanoma is seldom cured, even in patients who achieve a complete remission, because new sites of disease emerge. Autologous, proliferating, self-renewing tumor cells (putative tumor stem cells and/or early progenitor cells), are critical to establishment of new depots of metastatic cancer, and may be excellent sources of antigen for vaccines. These trials addressed the impact on survival from immunizing with antigens from such cells. Methods: Data was pooled from 3 successive phase II trials, all of which included patients with documented metastatic melanoma, who were treated in protocols that utilized antigens from cell cultures of autologous tumor cells. S.C. injections were given weekly for 3 weeks, then monthly for 5 months. 1992-2000: 74 patients were injected with irradiated tumor cells (TC). 2000-2006: 54 patients were injected with autologous dendritic cells (DC) that had been co-cultured with irradiated autologous tumor cells (NCI-V01-1646). 2007-2011: in a randomized phase II trial, 24 patients were injected with TC, and 18 with DC (NCT00436930). Results: The table summarizes overall survival (OS) in each trial. In the pooled analysis there were 98 TC and 72 DC patients. Characteristics were similar in terms of age (51, 52), male gender (62%, 62%), no evidence of disease at the time of treatment (46%, 47%), and presence of M1c visceral disease at the time of treatment (13%, 14%). OS was longer in patients treated with DC (median 63.1 vs 20.2 months, 5-year OS 51% vs 26%, p=0.0002 Mantle-Cox log-rank test). The difference in OS in the randomized trial is also significant (p=0.007). Conclusions: Patient-specific DC vaccines primed with antigens from autologous proliferating, self-renewing tumor cells are associated with encouraging long-term survival rates, and are superior to patient-specific TC vaccines in populations of patients who have been diagnosed with metastatic melanoma. [Table: see text]

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