A THERAPEUTIC NKT CELL ADJUVANT-BASED VACCINE INDUCES AN EFFECTIVE ANTITUMORAL IMMUNE RESPONSE IN B-CELL LYMPHOMA
(Abstract release date: 05/21/15)
EHA Library. Escribà L. 06/13/15; 103143; S468
Disclosure(s): Hospital de Sant Pau
Laura Escribà
Contributions
Contributions
Abstract
Abstract: S468
Type: Oral Presentation + travel grant
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room Stolz 2
Background
Aims
Methods
The murine B cell lymphoma line 4TOO was used as tumor model. A therapeutic vaccine was generated by mixing DCs and irradiated 4TOO tumor cells (106 cells in a 1:1 ratio) in the presence of α-GalCer (2μg/mouse). A single dose of the therapeutic vaccine was injected iv. into Balb/c mice (n=10 per group) two days after tumor challenge (4 x 105 cells/mouse, iv), and mice were followed for survival. NKT cell expansion was analyzed by flow cytometry using a PE conjugated CD1d: α-GalCer analogue (PBS-57) loaded tetramer (NIH Tetramer Core Facility, Atlanta GA). Intracellular IFN-γ production on NKT cells and CD4+ and CD8+ T cells was detected by flow cytometry. One-way ANOVA was used for comparisons between different experimental groups. Differences in survival were analyzed using the log-rank test.
Results
Therapeutic vaccine eradicated B cell lymphoma in all treated mice, and was superior to any vaccine combination, including α-GalCer alone, irradiated tumor cells with DCs, and DCs with α-GalCer (100%, 10%, 0% and 50% of survival at day 100, respectively; p<0.001). Importantly, 90% of treated mice with the vaccine were resistant to a tumor rechallenge, suggesting the development of a memory immune response. In addition, the immune response was tumor-specific since all the mice were unable to reject a syngeneic A20 B cell lymphoma. A significant NKT cell expansion in the spleen and liver of vaccinated mice was observed compared with control groups (4.8 vs. 1.2 fold expansion; p=0.02, and 3.8 vs 1.4 fold expansion; p=0.04, respectively). Moreover, this vaccination strategy induced an increase of IFN-γ secreting NKT cells (58.4% vs. 39.5% (p=0.05) and of IFN-γ secreting T cells compared to control groups (25.7% vs. 16.8% in CD8+ cells (p=0,04), and 31.2% vs. 14% in CD4+ cells (p=0,04).
Summary
A therapeutic vaccine consisting of dendritic cells pulsed with tumor cells plus the NKT agonist α-GalCer efficiently eradicates B cell lymphoma in a therapeutic setting. This immune response is long-lasting, tumor-specific, and it is associated with an expansion of NKT cells in lymphoid organs and with an increase in IFN-γ secreting NKT and T cells. These data support the development of immunotherapy strategies in patients with B cell lymphoma using DCs and NKT cell agonists.
Keyword(s): B cell lymphoma, Dendritic cell, Immunotherapy, NK-T cells
Session topic: Gene therapy, cellular immunotherapy and vaccination
Type: Oral Presentation + travel grant
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room Stolz 2
Background
Type I natural killer T (NKT) cells are lymphocytes with unique specificity for glycolipid antigens presented by nonpolymorphic CD1d receptor on dendritic cells (DCs). NKT cells play a central role in tumor immunology since they coordinate innate and adaptive immune responses. Activation of NKT cells with the prototypic lipid α-galactosylceramide (α-GalCer) stimulate INF-γ production and cytokine secretion (eg, IL-12, IL-17, IL-21) which contribute to the enhancement of T cell activation.
Aims
We evaluated the antitumor effect of a combination of DCs and irradiated tumor cells with the NKT cell agonist α-GalCer in a mouse model of B cell lymphoma.
Methods
The murine B cell lymphoma line 4TOO was used as tumor model. A therapeutic vaccine was generated by mixing DCs and irradiated 4TOO tumor cells (106 cells in a 1:1 ratio) in the presence of α-GalCer (2μg/mouse). A single dose of the therapeutic vaccine was injected iv. into Balb/c mice (n=10 per group) two days after tumor challenge (4 x 105 cells/mouse, iv), and mice were followed for survival. NKT cell expansion was analyzed by flow cytometry using a PE conjugated CD1d: α-GalCer analogue (PBS-57) loaded tetramer (NIH Tetramer Core Facility, Atlanta GA). Intracellular IFN-γ production on NKT cells and CD4+ and CD8+ T cells was detected by flow cytometry. One-way ANOVA was used for comparisons between different experimental groups. Differences in survival were analyzed using the log-rank test.
Results
Therapeutic vaccine eradicated B cell lymphoma in all treated mice, and was superior to any vaccine combination, including α-GalCer alone, irradiated tumor cells with DCs, and DCs with α-GalCer (100%, 10%, 0% and 50% of survival at day 100, respectively; p<0.001). Importantly, 90% of treated mice with the vaccine were resistant to a tumor rechallenge, suggesting the development of a memory immune response. In addition, the immune response was tumor-specific since all the mice were unable to reject a syngeneic A20 B cell lymphoma. A significant NKT cell expansion in the spleen and liver of vaccinated mice was observed compared with control groups (4.8 vs. 1.2 fold expansion; p=0.02, and 3.8 vs 1.4 fold expansion; p=0.04, respectively). Moreover, this vaccination strategy induced an increase of IFN-γ secreting NKT cells (58.4% vs. 39.5% (p=0.05) and of IFN-γ secreting T cells compared to control groups (25.7% vs. 16.8% in CD8+ cells (p=0,04), and 31.2% vs. 14% in CD4+ cells (p=0,04).
Summary
A therapeutic vaccine consisting of dendritic cells pulsed with tumor cells plus the NKT agonist α-GalCer efficiently eradicates B cell lymphoma in a therapeutic setting. This immune response is long-lasting, tumor-specific, and it is associated with an expansion of NKT cells in lymphoid organs and with an increase in IFN-γ secreting NKT and T cells. These data support the development of immunotherapy strategies in patients with B cell lymphoma using DCs and NKT cell agonists.
Keyword(s): B cell lymphoma, Dendritic cell, Immunotherapy, NK-T cells
Session topic: Gene therapy, cellular immunotherapy and vaccination
Abstract: S468
Type: Oral Presentation + travel grant
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room Stolz 2
Background
Aims
Methods
The murine B cell lymphoma line 4TOO was used as tumor model. A therapeutic vaccine was generated by mixing DCs and irradiated 4TOO tumor cells (106 cells in a 1:1 ratio) in the presence of α-GalCer (2μg/mouse). A single dose of the therapeutic vaccine was injected iv. into Balb/c mice (n=10 per group) two days after tumor challenge (4 x 105 cells/mouse, iv), and mice were followed for survival. NKT cell expansion was analyzed by flow cytometry using a PE conjugated CD1d: α-GalCer analogue (PBS-57) loaded tetramer (NIH Tetramer Core Facility, Atlanta GA). Intracellular IFN-γ production on NKT cells and CD4+ and CD8+ T cells was detected by flow cytometry. One-way ANOVA was used for comparisons between different experimental groups. Differences in survival were analyzed using the log-rank test.
Results
Therapeutic vaccine eradicated B cell lymphoma in all treated mice, and was superior to any vaccine combination, including α-GalCer alone, irradiated tumor cells with DCs, and DCs with α-GalCer (100%, 10%, 0% and 50% of survival at day 100, respectively; p<0.001). Importantly, 90% of treated mice with the vaccine were resistant to a tumor rechallenge, suggesting the development of a memory immune response. In addition, the immune response was tumor-specific since all the mice were unable to reject a syngeneic A20 B cell lymphoma. A significant NKT cell expansion in the spleen and liver of vaccinated mice was observed compared with control groups (4.8 vs. 1.2 fold expansion; p=0.02, and 3.8 vs 1.4 fold expansion; p=0.04, respectively). Moreover, this vaccination strategy induced an increase of IFN-γ secreting NKT cells (58.4% vs. 39.5% (p=0.05) and of IFN-γ secreting T cells compared to control groups (25.7% vs. 16.8% in CD8+ cells (p=0,04), and 31.2% vs. 14% in CD4+ cells (p=0,04).
Summary
A therapeutic vaccine consisting of dendritic cells pulsed with tumor cells plus the NKT agonist α-GalCer efficiently eradicates B cell lymphoma in a therapeutic setting. This immune response is long-lasting, tumor-specific, and it is associated with an expansion of NKT cells in lymphoid organs and with an increase in IFN-γ secreting NKT and T cells. These data support the development of immunotherapy strategies in patients with B cell lymphoma using DCs and NKT cell agonists.
Keyword(s): B cell lymphoma, Dendritic cell, Immunotherapy, NK-T cells
Session topic: Gene therapy, cellular immunotherapy and vaccination
Type: Oral Presentation + travel grant
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room Stolz 2
Background
Type I natural killer T (NKT) cells are lymphocytes with unique specificity for glycolipid antigens presented by nonpolymorphic CD1d receptor on dendritic cells (DCs). NKT cells play a central role in tumor immunology since they coordinate innate and adaptive immune responses. Activation of NKT cells with the prototypic lipid α-galactosylceramide (α-GalCer) stimulate INF-γ production and cytokine secretion (eg, IL-12, IL-17, IL-21) which contribute to the enhancement of T cell activation.
Aims
We evaluated the antitumor effect of a combination of DCs and irradiated tumor cells with the NKT cell agonist α-GalCer in a mouse model of B cell lymphoma.
Methods
The murine B cell lymphoma line 4TOO was used as tumor model. A therapeutic vaccine was generated by mixing DCs and irradiated 4TOO tumor cells (106 cells in a 1:1 ratio) in the presence of α-GalCer (2μg/mouse). A single dose of the therapeutic vaccine was injected iv. into Balb/c mice (n=10 per group) two days after tumor challenge (4 x 105 cells/mouse, iv), and mice were followed for survival. NKT cell expansion was analyzed by flow cytometry using a PE conjugated CD1d: α-GalCer analogue (PBS-57) loaded tetramer (NIH Tetramer Core Facility, Atlanta GA). Intracellular IFN-γ production on NKT cells and CD4+ and CD8+ T cells was detected by flow cytometry. One-way ANOVA was used for comparisons between different experimental groups. Differences in survival were analyzed using the log-rank test.
Results
Therapeutic vaccine eradicated B cell lymphoma in all treated mice, and was superior to any vaccine combination, including α-GalCer alone, irradiated tumor cells with DCs, and DCs with α-GalCer (100%, 10%, 0% and 50% of survival at day 100, respectively; p<0.001). Importantly, 90% of treated mice with the vaccine were resistant to a tumor rechallenge, suggesting the development of a memory immune response. In addition, the immune response was tumor-specific since all the mice were unable to reject a syngeneic A20 B cell lymphoma. A significant NKT cell expansion in the spleen and liver of vaccinated mice was observed compared with control groups (4.8 vs. 1.2 fold expansion; p=0.02, and 3.8 vs 1.4 fold expansion; p=0.04, respectively). Moreover, this vaccination strategy induced an increase of IFN-γ secreting NKT cells (58.4% vs. 39.5% (p=0.05) and of IFN-γ secreting T cells compared to control groups (25.7% vs. 16.8% in CD8+ cells (p=0,04), and 31.2% vs. 14% in CD4+ cells (p=0,04).
Summary
A therapeutic vaccine consisting of dendritic cells pulsed with tumor cells plus the NKT agonist α-GalCer efficiently eradicates B cell lymphoma in a therapeutic setting. This immune response is long-lasting, tumor-specific, and it is associated with an expansion of NKT cells in lymphoid organs and with an increase in IFN-γ secreting NKT and T cells. These data support the development of immunotherapy strategies in patients with B cell lymphoma using DCs and NKT cell agonists.
Keyword(s): B cell lymphoma, Dendritic cell, Immunotherapy, NK-T cells
Session topic: Gene therapy, cellular immunotherapy and vaccination
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