Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma

2021 ◽  
Vol 31 (4) ◽  
pp. 378-388
Author(s):  
Alexandra M. Adams ◽  
Robert C. Chick ◽  
Timothy J. Vreeland ◽  
Guy T. Clifton ◽  
Diane F. Hale ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Metastatic Melanoma ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Safety And Efficacy ◽  
Systemic Therapies

scholarly journals Comparison of Glioma-associated Antigen Peptide-loaded Versus Autologous Tumor Lysate-loaded Dendritic Cell Vaccination in Malignant Glioma Patients

2013 ◽  
Vol 36 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Robert M. Prins ◽  
Xiaoyan Wang ◽  
Horacio Soto ◽  
Emma Young ◽  
Dominique N. Lisiero ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Malignant Glioma ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Antigen Peptide

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.

Clinical efficacy of vaccination with the autologous tumor lysate particle loaded dendritic cell (TLPLDC) vaccine in metastatic melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21025-e21025
Author(s):  
Annelies Hickerson ◽  
Guy T. Clifton ◽  
Tommy A Brown ◽  
Jessica Campf ◽  
John William Myers ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Metastatic Melanoma ◽  
Ex Vivo ◽  
Objective Response ◽  
Complete Response ◽  
Intradermal Injection ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Open Label ◽  
Measurable Disease

e21025 Background: The treatment of melanoma has changed drastically with the advent of immunotherapy. The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine stimulates T-cells and may work synergistically with other immunotherapies. Here, we describe results in patients (pts) with metastatic melanoma (MM) treated with the TLPLDC vaccine together with other approved therapies. Methods: The TLPLDC vaccine is created using autologous tumor lysate loaded yeast cell wall particles to prime autologous dendritic cells ex-vivo. 1-1.5x106 TLPLDCs are given via intradermal injection monthly x 4 followed by boosters at six and nine months (mo). Pts who recurred while enrolled in our adjuvant phase IIb trial of the TLPLDC vaccine and pts with MM with measurable disease enrolled in a separate phase I/IIa trial were offered vaccination of TLPLDC vaccine in an open-label fashion in addition to other approved therapies as determined by their treating physician. Tumor response is measured by RECIST 1.1 criteria. Results: To date, 50 pts have been enrolled in the two trials (25 pts in each). Of the 42 pts with measureable disease, 30 pts received at least one dose of the vaccine, 11 progressed prior to vaccine administration, and 1 is pending. 2 pts withdrew at 2 and 7 mo. Of the remaining 28 evaluable pts, 13 pts had progressive disease with a median follow-up (f/u) of 3 (range 0-12) mo, 12 pts had stable disease with a median f/u of 7.5 (range 1-23) mo, 2 pts had a partial response with f/u of 7 and 13 mo, and one pt had a complete response with 18 mo of f/u. Overall, in pts with measureable disease, the disease control rate was 54% (15/28) and objective response rate was 11% (3/28). 8 pts were without measurable disease at enrollment, 3 recurred at a median f/u of 8 mo and 5 remain disease-free at a median of 26 mo f/u. No grade ≥ 3 toxicities were observed with combination TLPLDC vaccination and approved systemic therapies. Conclusions: Vaccination with the TLPLDC vaccine in combination with systemic approved therapies in MM pts is well tolerated and may provide clinical benefit in patients with and without measurable disease. Clinical trial information: NCT02678741.

scholarly journals IMMU-10. INTERIM ANALYSIS OF THE HIT-HGG REZ IMMUNVAC STUDY - DENDRITIC CELL VACCINATION WITH PARTIAL TREG DEPLETION IN CHILDREN, ADOLESCENTS, AND ADULTS WITH RELAPSED HIGH-GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii361-iii361
Author(s):  
Matthias Eyrich ◽  
Jürgen Krauss ◽  
Johannes Rachor ◽  
Camelia Monoranu ◽  
Brigitte Bison ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
T Cell Response ◽  
High Rate ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
High Grade ◽  
Tumor Lysate ◽  
Treg Depletion ◽  
High Grade Gliomas ◽  
Over Time

Abstract Efficacy of therapeutic dendritic cell vaccines (DCV) can be limited by immunosuppressive mechanisms in the micromilieu of high-grade gliomas. In the HIT-HGG-Rez Immunovac trial (Eudra-CT 2013-000419-26), we investigate whether a reduction of Treg with metronomic cyclophosphamide (metrCyc) might be a feasible option to improve vaccine efficacy. 10 pediatric (mean age 11.4±4.2y) and 5 adult patients (mean age 39.5±19.9y) with relapsed glioblastoma were treated according to the HIT-HGG-Rez Immunovac protocol so far. 2 children were treated within the trial, the other 13 in the pilot phase. Patients received upfront oral metrCyc for 2–4 weeks. After reoperation and monocyte-apheresis, patients received 4 weekly intradermal doses of autologous, TNFa/IL-1ß matured DCs pulsed with tumor lysate in imiquimod-prepared skin. Thereafter, tumor lysate boosts were given. All patients received at least 5 vaccines (4xDCs, 1xlysate boosts). MetrCyc was well tolerated and led to a reduction in Treg-frequency of 35.6±17.8% followed by a rebound after cessation of metrCyc. Importantly, 13/14 analyzed patients showed a positive IFNg-T-cell response against autologous tumor lysate with a tendency to decrease over time. 6-month overall survival was 100%, compared to 65% in a historical control. Mean PFS and OS were 5.7 and 21.1 months with no difference between adults and children. We conclude that DCV in combination with partial Treg depletion is feasible, safe, and related with a high rate of tumor-specific IFNg-responses. As the clinically and immunologically beneficial effects seem to diminish over time, we aim to combine our approach with checkpoint inhibition in the next amendment.

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