Delving into the Latest Updates on Dendritic Cell Vaccine(H. Lee Moffitt Cancer Center and Research Institute) with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine, Dendritic cell vaccine

Synonyms-

Target

HER2 x HER3

Action

modulators, stimulants

Mechanism

HER2 modulators(Receptor protein-tyrosine kinase erbB-2 modulators), HER3 modulators(Receptor tyrosine-protein kinase erbB-3 modulators), Immunostimulants

Therapeutic Areas

NeoplasmsNervous System DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication

HER2 Positive Breast CancerMeningeal NeoplasmsER-low Breast cancer+ [2]

Inactive Indication-

Originator Organization

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Active Organization

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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RATIONALEGlioblastoma is one of the most aggressive human brain tumors. The prognosis is unfavorable and treatment effects are relatively low. However, temozolomide (TMZ) chemotherapy may prolong patients' survival.OBJECTIVE OF THE PAPERThe anti-glioma effect of clofazimine used in immunotherapy is examined in vivo.MATERIALS AND METHODSMethod of obtaining TMZ-resistant GB cells included treatment of T98G glioblastoma cells with 150 μmol/l TMZ. To confirm resistance to TMZ, MTT assay was performed according to the manufacturer's protocol. Untreated cells were used as a control group. C6 glioma cells were stereotactically implanted into the brain of Wistar rats and irradiated (24 Gy) in combination with oral administration of TMZ (20 mg/ kg) and clofazimine (CFZ) (30 mg/kg). This was followed by subsequent immunotherapy including tumor cell and dendritic cell vaccines. Neurovisualisation, immunocytochemical and immunohistochemical assays were used and animals' survival was analyzed with Kaplan-Meier estimator.RESULTST98G resistant glioblastoma cell line is characterized by immunoreactive β-catenin, CD133, CD44, and N-cadherin as compared to the control cell line. The IC 50 of clofazimine for T98G glioblastoma cell line is 38.3 ± 4,1 μmol/l, for C6 rat glioma cell line is 37,6 ± 3,2 μmol/l. Clofazimine enhanced the cytotoxic activity of temozolomide, paclitaxel, and carboplatin in cancer cells of T98G line as compared to the control group. The cytotoxic effect of lomustine and carboplatin against T98G resistant glioblastoma cells was also enhanced by Clofazimine. Tumor cell vaccine (TCV) and dendritic cell vaccine (DCV) in combination with clofazimine produces a stronger anti-tumor immune response in C6 glioma. This is evident with development of local inflammatory reaction with higher content of interleukin 1β and 18 in serum, as well as greater level of IBA1+, CD68 + in pro-inflammatory microglia of neoplastic tissues. Combined use of DCV and clofazimine results in higher survival rates in experimental animals (- 90 ± 7 days against 45 ± 5 days) in the treated group with chemoradiation therapy (CRT).CONCLUSIONSCombination of clofazimine and immunotherapy enhances anti-glioma effect of TMZ in an in vivo model experiment.

15 Oct 2024·International Journal of Cancer

Personalized dendritic cell vaccine in multimodal individualized combination therapy improves survival in high‐risk pediatric cancer patients

Article

Author: Hlavackova, Eva ; Dusek, Vitezslav ; Kubatova, Jana ; Jezova, Marta ; Mazanek, Pavel ; Dubska, Lenka Zdrazilova ; Demlova, Regina ; Polaskova, Kristyna ; Vejmelkova, Klara ; Kuttnerova, Zuzana ; Palova, Hana ; Pokorna, Petra ; Balaz, Martin ; Turekova, Terezia ; Mlnarikova, Marie ; Pavelka, Zdenek ; Mudry, Peter ; Slaby, Ondrej ; Sterba, Jaroslav ; Pilatova, Katerina Cerna ; Kyr, Michal ; Valik, Dalibor ; Tinka, Pavel ; Kozakova, Sarka ; Kellnerova, Renata ; Merta, Tomas

AbstractA lot of hope for high‐risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single‐agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high‐risk solid tumors using the N‐of‐1 approach in real‐world scenario. A total of 160 evaluable events occurred in 48 patients during the 4‐year follow‐up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check‐point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.

01 May 2024·Cell Reports Medicine

Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum

Article

Author: Lootens, Nele ; Billiet, Lore ; Vandekerckhove, Bart ; Roelandt, Ria ; Menten, Björn ; Vantomme, Lies ; Pille, Melissa ; Bonte, Sarah ; Dhondt, Annemieke ; De Munter, Stijn ; Deseins, Lucas ; Van Houtte, Eva ; Vanommeslaeghe, Floris ; Impens, Francis ; Leclercq, Georges ; Vermijlen, David ; Taghon, Tom ; Goetgeluk, Glenn ; Van Lint, Sandra ; Weening, Karin ; Eekhout, Thomas ; Verstraete, Tasja ; Théry, Fabien ; Kerre, Tessa ; Van Dorpe, Jo ; Vandamme, Niels ; Pascal, Eva ; Brusseel, Marieke ; De Smet, Saskia ; De Cock, Laurenz ; Devreker, Pam ; Surmont, Veerle ; Buyle, Jolien ; Mayer, Rupert L ; Ferdinande, Liesbeth ; De Ryck, Frederic ; Heyns, Kelly ; Vermaelen, Karim ; Verdonckt, Maarten ; Ingels, Joline ; Stevens, Dieter ; Sanchez, Guillem Sanchez ; Desender, Liesbeth ; Jansen, Hanne ; Vermassen, Frank

Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination. Single-cell analysis indicates that the responsive T cell population is polyclonal and exhibits the near-entire spectrum of T cell differentiation states, including a naive-like state, but excluding exhausted cell states. Three of six vaccinated patients experience disease recurrence during the follow-up period of 2 years. Collectively, these data support the feasibility, safety, and immunogenicity of this treatment in resected NSCLC.

100 Deals associated with Dendritic Cell Vaccine(H. Lee Moffitt Cancer Center and Research Institute)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2 Positive Breast Cancer	Phase 1	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	22 Aug 2023
Meningeal Neoplasms	Phase 1	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	22 Aug 2023
ER-low Breast cancer	Phase 1	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	26 Aug 2022
HER2-negative breast cancer	Phase 1	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	26 Aug 2022
Triple Negative Breast Cancer	Phase 1	United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	26 Aug 2022