Induction of T cell precursors in advanced melanoma treated with autologous tumor lysate loaded dendritic cells

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2623-2623
Author(s):  
T. S. Crocenzi ◽  
C. G. Tretter ◽  
J. Fisher ◽  
N. Crosby ◽  
D. Truman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Advanced Melanoma ◽  
Autologous Tumor ◽  
Tumor Lysate

Induction of T cell precursors in advanced melanoma treated with autologous tumor lysate loaded dendritic cells

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2623-2623
Author(s):  
T. S. Crocenzi ◽  
C. G. Tretter ◽  
J. Fisher ◽  
N. Crosby ◽  
D. Truman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Advanced Melanoma ◽  
Autologous Tumor ◽  
Tumor Lysate

Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate–pulsed dendritic cells

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2338-2344 ◽  
Author(s):  
Tanja Maier ◽  
Adrian Tun-Kyi ◽  
Anatoli Tassis ◽  
Karl-Peter Jungius ◽  
Günter Burg ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Delayed Type Hypersensitivity ◽  
Interferon Α ◽  
Autologous Tumor ◽  
Cutaneous T Cell Lymphoma ◽  
Tumor Lysate

Abstract Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative skin disease with limited therapeutic options. Ten CTCL patients were treated with once-weekly intranodal injection of 1 × 106 mature monocyte-derived dendritic cells (DCs) pulsed with 100 μg/mL tumor lysate protein equivalent and keyhole limpet hemocyanin (50 μg/mL). Tumor-specific delayed-type hypersensitivity (DTH) reactions developed in 8 of 8 patients challenged with tumor-lysate-pulsed DCs and in 3 of 8 patients challenged with tumor lysate alone. Three of 5 patients showed significant tumor-lysate-specific increases of in vitro peripheral blood lymphocyte proliferation coinciding with increased interferon-α (IFN-α) production. Five of 10 (50%) patients had objective responses. Four patients had partial responses (PRs). Two are still in PR, and the other 2 patients had a mean PR duration of 10.5 months. One patient had a complete response (CR) for 19 months that is ongoing. The remaining 5 patients had progressive disease. In the 5 responder patients, 6.8 ± 1.4 vaccinations were necessary to induce an objective clinical response. Response was associated with low tumor burden. Continuation of vaccinations with new tumor lysate derived from progressive lesions reinduced treatment responses in 2 patients in PR. Selected patients had massive infiltration of CD8+ and TIA+ cytotoxic T cells at the site of regressing lesions and molecular remission after therapy. Intranodal injection of autologous tumor-lysate-pulsed DCs is well-tolerated and achieves immunologic and objective clinical responses in selected CTCL patients. (Blood. 2003;102:2338-2344)

Allogeneic partially HLA-matched dendritic cells (DC) as a vaccine in metastatic renal cell cancer (mRCC): Final analysis of a clinical phase I/II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15053-e15053 ◽  
Author(s):  
Anne Flörcken ◽  
Joachim Kopp ◽  
Kamran Movassaghi ◽  
Antje van Lessen ◽  
Anna Takvorian ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Clinical Response ◽  
Cell Cancer ◽  
T Cell Responses ◽  
T Cell Response ◽  
Delayed Type Hypersensitivity ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Cell Responses

e15053 Background: Despite novel kinase inhibitors, prognosis of metastatic RCC remains poor and new experimental approaches are warranted. Our aim was to evaluate a DC-based vaccine, which exploits alloreactivity as a means to amplify specific anti-tumor immune responses. Methods: Allogeneic, partially HLA-matched DC were generated in our GMP facility. DC were loaded with autologous tumor lysate. 8 patients with progressive mRCC were included, 7 patients were immunized repetitively with 107 DC s.c. over 20 weeks. Low-dose IL-2 (3 Mio U s.c. qd) was used concomitantly. Endpoints of the study were feasibility, safety, immunological and clinical responses. T cell responses against HLA-A2-restricted RCC-associated antigens were evaluated by proliferation assays, ELISpot and cytokine bead array (CBA). T cell repertoire was analysed by T cell receptor γ and –β PCR. Results: Vaccination was feasible and safe, no treatment-related grade 3/4 toxicity or clinically relevant autoimmunity was observed. No objective responses were observed, however, 2/7 patients showed stable disease, one a minimal clinical response. The mean TTP was 24.6 weeks (range 5 to 96). Delayed-type hypersensitivity was detected in 3/7 and HLA antibodies were induced in 3/7 patients. In 3/7 patients T cell responses against RCC-associated antigens such as TYMS, G250, vimentin, surviving and cyclin-D1 were induced by vaccination. These antigen-specific T cells showed a predominant TH1-cytokine profile. Interestingly, a clonally expanded T cell population could be detected by γ- and –β PCR in one patient with both a minimal clinical response and a T cell response. This clone is currently persisting for more than 80 months, its specificity is under investigation. Conclusions: Vaccination with allogeneic tumor-lysate-loaded DC was feasible, safe and was able to induce TH1-polarized immune responses against RCC-associated antigens. Tumor vaccination might be a promising approach in minimal residual disease, possibly in combination with antibodies against CTLA-4 or PD-1.

A prospective, randomized, blinded, placebo-controlled, phase IIb trial of an autologous tumor lysate + yeast cell wall particles (YCWP) + dendritic cells (DC) vaccine vs unloaded YCWP + DC and embedded phase I/IIa trial with tumor lysate particle only (TLPO) vaccine in stage III and stage IV (resected) melanoma to prevent recurrence.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS201-TPS201 ◽  
Author(s):  
John W Myers ◽  
Garth S Herbert ◽  
Guy T Clifton ◽  
Timothy J Vreeland ◽  
Tommy A Brown ◽  
...  
Keyword(s):  
Cell Wall ◽  
Dendritic Cells ◽  
High Risk ◽  
Yeast Cell ◽  
Yeast Cell Wall ◽  
Stage Iii ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Risk Of Recurrence ◽  
Disease Free

TPS201 Background: Melanoma is a potentially lethal skin malignancy; patients with stage III/IV resected disease have a recurrence rate of 50-90%. Adjuvant checkpoint inhibitor immunotherapy decreases the risk of recurrence but also causes significant immune-related toxicity. Vaccines are a promising strategy for patients with high risk melanoma. The optimal time to intervene may be in the adjuvant setting after attaining a disease-free state through standard of care therapies. Our strategy uses autologous tumor lysate (TL) in a yeast cell wall particle (YCWP) to load dendritic cells (DC) ex vivo. The tumor lysate particle loaded dendritic cell (TLPLDC) vaccine is then given to prevent melanoma recurrences. An alternate vaccine delivery method that we are evaluating utilizes the tumor lysate particle-only (TLPO) technique, in which tumor lysate is loaded into capped YCWP and injected intradermally, allowing an in vivo uptake by the patient’s dendritic cells. Methods: We are performing a prospective, randomized, blinded, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma who have been rendered disease-free but remain at high risk of recurrence. The study will utilize the TLPLDC strategy vs placebo (2:1) in 120 patients, followed by a bridging study of TLPO vs TLPLDC (2:1) in 60 patients. Both TLPLDC and TLPO inoculations will be monthly x3, followed by boosters at 6, 12, and 18 months. Primary endpoints will be disease free survival (DFS) at 24 months in the TLPLDC arm, and overall safety in the TLPO arm. We have completed enrollment in the phase IIb portion of the study. Clinical trial information: NCT02301611.

scholarly journals PGE2 Is Crucial for the Generation of FAST Whole- Tumor-Antigens Loaded Dendritic Cells Suitable for Immunotherapy in Glioblastoma

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 215
Author(s):  
Sara Nava ◽  
Daniela Lisini ◽  
Simona Frigerio ◽  
Simona Pogliani ◽  
Serena Pellegatta ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Large Scale ◽  
Tumor Antigens ◽  
Labor Cost ◽  
Small Scale ◽  
Clinical Grade ◽  
Tumor Lysate

Dendritic cells (DC) are the most potent antigen-presenting cells, strongly inducers of T cell-mediated immune responses and, as such, broadly used as vaccine adjuvant in experimental clinical settings. DC are widely generated from human monocytes following in vitro protocols which require 5–7 days of differentiation with GM-CSF and IL-4 followed by 2–3 days of activation/maturation. In attempts to shorten the vaccine’s production, Fast-DC protocols have been developed. Here we reported a Fast-DC method in compliance with good manufacturing practices for the production of autologous mature dendritic cells loaded with antigens derived from whole tumor lysate, suitable for the immunotherapy in glioblastoma patients. The feasibility of generating Fast-DC pulsed with whole tumor lysate was assessed using a series of small-scale cultures performed in parallel with clinical grade large scale standard method preparations. Our results demonstrate that this Fast protocol is effective only in the presence of PGE2 in the maturation cocktail to guarantee that Fast-DC cells exhibit a mature phenotype and fulfill all requirements for in vivo use in immunotherapy approaches. Fast-DC generated following this protocol were equally potent to standard DC in inducing Ag-specific T cell proliferation in vitro. Generation of Fast-DC not only reduces labor, cost, and time required for in vitro clinical grade DC development, but can also minimizes inter-preparations variability and the risk of contamination.

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.

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