IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY

Amber Giles; Leonard Nettey; Thomas Liechti; Margaret Beddall; Elizabeth Vera; Deric Park; Jing Wu; Brett Theeler; Christine Siegel; Lisa Boris; Nancy Garren; Christine Bryla; Ann McCoy; Edjah Nduom; Kareem Zaghloul; Terri Armstrong; Mario Roederer; Mark Gilbert

doi:10.1093/neuonc/noy148.571

IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY

Amber Giles, Leonard Nettey, Thomas Liechti, Margaret Beddall, Elizabeth Vera, Deric Park, Jing Wu, Brett Theeler, Christine Siegel, Lisa Boris, Nancy Garren, Christine Bryla, Ann McCoy, Edjah Nduom, Kareem Zaghloul, Terri Armstrong, Mario Roederer, Mark Gilbert

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

s vi137 NEURO-ONCOLOGY • NOVEMBER 2018 suppress immunity, but rather, heightened interferon-(IFN)-γ reactivity. Addition of ICIs (to animals primed with RNA-NPs) augmented periph-eral/intratumoral PD-1+CD8+ cells and mediated synergistic anti-tumor efficacy in settings where ICIs alone did not confer therapeutic benefit. These synergistic effects were mediated by type-I-interferon released from PD-L1+ plasmacytoid dendritic-cells. In translational studies, personal-ized mRNA-NPs (from whole tumor-transcriptome) were safe and active in a client-owned canine with a spontaneous malignant glioma. In this patient, RNA-NPs elicited robust immunologic activity with increased percentages of activated PD-L1+ APCs and IFNγ+CD8+ cells. CONCLUSION: RNA-NPs elicit widespread immune activation concomitant with inducible PD-L1 expression on intratumoral APCs that can be therapeutically exploited. Since RNA-NPs bypass cost/complexity of cellular thera-peutics, are amenable to central distribution, and can be made within days of tumor resection, these formulations can be expeditiously translated as biomodulators of GBM immunogenicity.

Original language	American English
Pages (from-to)	vi137-vi137
Journal	Neuro-Oncology
Volume	20
Issue number	suppl_6
DOIs	https://doi.org/10.1093/neuonc/noy148.571
State	Published - May 2018

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10.1093/neuonc/noy148.571

Cite this

Giles, A., Nettey, L., Liechti, T., Beddall, M., Vera, E., Park, D., Wu, J., Theeler, B., Siegel, C., Boris, L., Garren, N., Bryla, C., McCoy, A., Nduom, E., Zaghloul, K., Armstrong, T., Roederer, M., & Gilbert, M. (2018). IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY. Neuro-Oncology, 20(suppl_6), vi137-vi137. https://doi.org/10.1093/neuonc/noy148.571

@article{be5bc446fdb3421db62611ce58a1eef9,

title = "IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY",

abstract = "s vi137 NEURO-ONCOLOGY • NOVEMBER 2018 suppress immunity, but rather, heightened interferon-(IFN)-γ reactivity. Addition of ICIs (to animals primed with RNA-NPs) augmented periph-eral/intratumoral PD-1+CD8+ cells and mediated synergistic anti-tumor efficacy in settings where ICIs alone did not confer therapeutic benefit. These synergistic effects were mediated by type-I-interferon released from PD-L1+ plasmacytoid dendritic-cells. In translational studies, personal-ized mRNA-NPs (from whole tumor-transcriptome) were safe and active in a client-owned canine with a spontaneous malignant glioma. In this patient, RNA-NPs elicited robust immunologic activity with increased percentages of activated PD-L1+ APCs and IFNγ+CD8+ cells. CONCLUSION: RNA-NPs elicit widespread immune activation concomitant with inducible PD-L1 expression on intratumoral APCs that can be therapeutically exploited. Since RNA-NPs bypass cost/complexity of cellular thera-peutics, are amenable to central distribution, and can be made within days of tumor resection, these formulations can be expeditiously translated as biomodulators of GBM immunogenicity.",

author = "Amber Giles and Leonard Nettey and Thomas Liechti and Margaret Beddall and Elizabeth Vera and Deric Park and Jing Wu and Brett Theeler and Christine Siegel and Lisa Boris and Nancy Garren and Christine Bryla and Ann McCoy and Edjah Nduom and Kareem Zaghloul and Terri Armstrong and Mario Roederer and Mark Gilbert",

year = "2018",

month = may,

doi = "10.1093/neuonc/noy148.571",

language = "American English",

volume = "20",

pages = "vi137--vi137",

journal = "Neuro-Oncology",

issn = "1522-8517",

number = "suppl_6",

}

Giles, A, Nettey, L, Liechti, T, Beddall, M, Vera, E, Park, D, Wu, J, Theeler, B, Siegel, C, Boris, L, Garren, N, Bryla, C, McCoy, A, Nduom, E, Zaghloul, K, Armstrong, T, Roederer, M & Gilbert, M 2018, 'IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY', Neuro-Oncology, vol. 20, no. suppl_6, pp. vi137-vi137. https://doi.org/10.1093/neuonc/noy148.571

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T1 - IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY

AU - Giles, Amber

AU - Nettey, Leonard

AU - Liechti, Thomas

AU - Beddall, Margaret

AU - Vera, Elizabeth

AU - Park, Deric

AU - Wu, Jing

AU - Theeler, Brett

AU - Siegel, Christine

AU - Boris, Lisa

AU - Garren, Nancy

AU - Bryla, Christine

AU - McCoy, Ann

AU - Nduom, Edjah

AU - Zaghloul, Kareem

AU - Armstrong, Terri

AU - Roederer, Mario

AU - Gilbert, Mark

PY - 2018/5

Y1 - 2018/5

N2 - s vi137 NEURO-ONCOLOGY • NOVEMBER 2018 suppress immunity, but rather, heightened interferon-(IFN)-γ reactivity. Addition of ICIs (to animals primed with RNA-NPs) augmented periph-eral/intratumoral PD-1+CD8+ cells and mediated synergistic anti-tumor efficacy in settings where ICIs alone did not confer therapeutic benefit. These synergistic effects were mediated by type-I-interferon released from PD-L1+ plasmacytoid dendritic-cells. In translational studies, personal-ized mRNA-NPs (from whole tumor-transcriptome) were safe and active in a client-owned canine with a spontaneous malignant glioma. In this patient, RNA-NPs elicited robust immunologic activity with increased percentages of activated PD-L1+ APCs and IFNγ+CD8+ cells. CONCLUSION: RNA-NPs elicit widespread immune activation concomitant with inducible PD-L1 expression on intratumoral APCs that can be therapeutically exploited. Since RNA-NPs bypass cost/complexity of cellular thera-peutics, are amenable to central distribution, and can be made within days of tumor resection, these formulations can be expeditiously translated as biomodulators of GBM immunogenicity.

AB - s vi137 NEURO-ONCOLOGY • NOVEMBER 2018 suppress immunity, but rather, heightened interferon-(IFN)-γ reactivity. Addition of ICIs (to animals primed with RNA-NPs) augmented periph-eral/intratumoral PD-1+CD8+ cells and mediated synergistic anti-tumor efficacy in settings where ICIs alone did not confer therapeutic benefit. These synergistic effects were mediated by type-I-interferon released from PD-L1+ plasmacytoid dendritic-cells. In translational studies, personal-ized mRNA-NPs (from whole tumor-transcriptome) were safe and active in a client-owned canine with a spontaneous malignant glioma. In this patient, RNA-NPs elicited robust immunologic activity with increased percentages of activated PD-L1+ APCs and IFNγ+CD8+ cells. CONCLUSION: RNA-NPs elicit widespread immune activation concomitant with inducible PD-L1 expression on intratumoral APCs that can be therapeutically exploited. Since RNA-NPs bypass cost/complexity of cellular thera-peutics, are amenable to central distribution, and can be made within days of tumor resection, these formulations can be expeditiously translated as biomodulators of GBM immunogenicity.

UR - https://www.mendeley.com/catalogue/18cbbbdb-a565-3ede-9616-8c99323ecb1e/

U2 - 10.1093/neuonc/noy148.571

DO - 10.1093/neuonc/noy148.571

M3 - Article

SN - 1522-8517

VL - 20

SP - vi137-vi137

JO - Neuro-Oncology

JF - Neuro-Oncology

IS - suppl_6

ER -