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Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses

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Harvard

Dey, S, Sutanto-Ward, E, Kopp, KL, DuHadaway, J, Mondal, A, Ghaban, D, Lecoq, I, Zocca, M-B, Merlo, LMF, Mandik-Nayak, L, Andersen, MH, Pedersen, AW & Muller, AJ 2020, 'Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses', Journal for ImmunoTherapy of Cancer, bind 8, nr. 2, 2020000605. https://doi.org/10.1136/jitc-2020-000605

APA

Dey, S., Sutanto-Ward, E., Kopp, K. L., DuHadaway, J., Mondal, A., Ghaban, D., Lecoq, I., Zocca, M-B., Merlo, L. M. F., Mandik-Nayak, L., Andersen, M. H., Pedersen, A. W., & Muller, A. J. (2020). Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses. Journal for ImmunoTherapy of Cancer, 8(2), [2020000605]. https://doi.org/10.1136/jitc-2020-000605

CBE

Dey S, Sutanto-Ward E, Kopp KL, DuHadaway J, Mondal A, Ghaban D, Lecoq I, Zocca M-B, Merlo LMF, Mandik-Nayak L, Andersen MH, Pedersen AW, Muller AJ. 2020. Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses. Journal for ImmunoTherapy of Cancer. 8(2):Article 2020000605. https://doi.org/10.1136/jitc-2020-000605

MLA

Vancouver

Author

Dey, Souvik ; Sutanto-Ward, Erika ; Kopp, Katharina L ; DuHadaway, James ; Mondal, Arpita ; Ghaban, Dema ; Lecoq, Inés ; Zocca, Mai-Britt ; Merlo, Lauren M F ; Mandik-Nayak, Laura ; Andersen, Mads Hald ; Pedersen, Ayako Wakatsuki ; Muller, Alexander J. / Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses. I: Journal for ImmunoTherapy of Cancer. 2020 ; Bind 8, Nr. 2.

Bibtex

@article{2ac5792bdff24f4284865e7d69e9634a,
title = "Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses",
abstract = "BACKGROUND: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been interpreted as counterbalancing IDO1-mediated immunosuppression. Based on this hypothesis, clinical studies employing an IDO1 peptide-based vaccine approach for cancer treatment have been initiated, but there remains a pressing need to further investigate the immunological ramifications of stimulating the anti-IDO1 T-cell response in this manner.METHODS: CT26 colon carcinoma tumors were evaluated for expression of IDO1 protein by western blot analysis, immunofluorescence microscopy and flow cytometry. Mouse IDO1-derived peptides, predicted to bind either major histocompatibility complex (MHC) class I or II of the H2d BALB/c strain, were emulsified in 50% Montanide for prophylactic or therapeutic vaccine treatment of CT26 tumor-bearing mice initiated either 7 days prior to or following tumor cell injection, respectively. In some therapeutic treatment experiments, administration of programmed cell death protein 1-binding antibody (anti-PD1 antibody) or epacadostat was concurrently initiated. Tumor size was determined by caliper measurements and comparative tumor growth suppression was assessed by longitudinal analyses of tumor growth data. For adoptive transfer, T cells from complete responder animals were isolated using paramagnetic beads and fluorescence-activated cell sorting.RESULTS: This study identifies mouse MHC class I-directed and II-directed, IDO1-derived peptides capable of eliciting antitumor responses, despite finding IDO1 expressed exclusively in tumor-infiltrating immune cells. Treatment of established tumors with anti-PD1 antibody and class I-directed but not class II-directed IDO1 peptide vaccines produced an enhanced antitumor response. Likewise, class I-directed and II-directed IDO1 peptides elicited an enhanced combinatorial response, suggesting distinct mechanisms of action. Consistent with this interpretation, adoptive transfer of isolated CD8+ T cells from class I and CD4+ T cells from class II peptide-vaccinated responder mice delayed tumor growth. The class II-directed response was completely IDO1-dependent while the class I-directed response included an IDO1-independent component consistent with antigen spread.CONCLUSIONS: The in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlight the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy.",
keywords = "adaptive immunity, immunotherapy, indoleamine-pyrrole 2,3,-dioxygenase, programmed cell death 1 receptor, vaccination",
author = "Souvik Dey and Erika Sutanto-Ward and Kopp, {Katharina L} and James DuHadaway and Arpita Mondal and Dema Ghaban and In{\'e}s Lecoq and Mai-Britt Zocca and Merlo, {Lauren M F} and Laura Mandik-Nayak and Andersen, {Mads Hald} and Pedersen, {Ayako Wakatsuki} and Muller, {Alexander J}",
note = "{\textcopyright} Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2020",
month = jul,
doi = "10.1136/jitc-2020-000605",
language = "English",
volume = "8",
journal = "Journal for ImmunoTherapy of Cancer",
issn = "2051-1426",
publisher = "BioMed Central",
number = "2",

}

RIS

TY - JOUR

T1 - Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses

AU - Dey, Souvik

AU - Sutanto-Ward, Erika

AU - Kopp, Katharina L

AU - DuHadaway, James

AU - Mondal, Arpita

AU - Ghaban, Dema

AU - Lecoq, Inés

AU - Zocca, Mai-Britt

AU - Merlo, Lauren M F

AU - Mandik-Nayak, Laura

AU - Andersen, Mads Hald

AU - Pedersen, Ayako Wakatsuki

AU - Muller, Alexander J

N1 - © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/7

Y1 - 2020/7

N2 - BACKGROUND: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been interpreted as counterbalancing IDO1-mediated immunosuppression. Based on this hypothesis, clinical studies employing an IDO1 peptide-based vaccine approach for cancer treatment have been initiated, but there remains a pressing need to further investigate the immunological ramifications of stimulating the anti-IDO1 T-cell response in this manner.METHODS: CT26 colon carcinoma tumors were evaluated for expression of IDO1 protein by western blot analysis, immunofluorescence microscopy and flow cytometry. Mouse IDO1-derived peptides, predicted to bind either major histocompatibility complex (MHC) class I or II of the H2d BALB/c strain, were emulsified in 50% Montanide for prophylactic or therapeutic vaccine treatment of CT26 tumor-bearing mice initiated either 7 days prior to or following tumor cell injection, respectively. In some therapeutic treatment experiments, administration of programmed cell death protein 1-binding antibody (anti-PD1 antibody) or epacadostat was concurrently initiated. Tumor size was determined by caliper measurements and comparative tumor growth suppression was assessed by longitudinal analyses of tumor growth data. For adoptive transfer, T cells from complete responder animals were isolated using paramagnetic beads and fluorescence-activated cell sorting.RESULTS: This study identifies mouse MHC class I-directed and II-directed, IDO1-derived peptides capable of eliciting antitumor responses, despite finding IDO1 expressed exclusively in tumor-infiltrating immune cells. Treatment of established tumors with anti-PD1 antibody and class I-directed but not class II-directed IDO1 peptide vaccines produced an enhanced antitumor response. Likewise, class I-directed and II-directed IDO1 peptides elicited an enhanced combinatorial response, suggesting distinct mechanisms of action. Consistent with this interpretation, adoptive transfer of isolated CD8+ T cells from class I and CD4+ T cells from class II peptide-vaccinated responder mice delayed tumor growth. The class II-directed response was completely IDO1-dependent while the class I-directed response included an IDO1-independent component consistent with antigen spread.CONCLUSIONS: The in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlight the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy.

AB - BACKGROUND: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been interpreted as counterbalancing IDO1-mediated immunosuppression. Based on this hypothesis, clinical studies employing an IDO1 peptide-based vaccine approach for cancer treatment have been initiated, but there remains a pressing need to further investigate the immunological ramifications of stimulating the anti-IDO1 T-cell response in this manner.METHODS: CT26 colon carcinoma tumors were evaluated for expression of IDO1 protein by western blot analysis, immunofluorescence microscopy and flow cytometry. Mouse IDO1-derived peptides, predicted to bind either major histocompatibility complex (MHC) class I or II of the H2d BALB/c strain, were emulsified in 50% Montanide for prophylactic or therapeutic vaccine treatment of CT26 tumor-bearing mice initiated either 7 days prior to or following tumor cell injection, respectively. In some therapeutic treatment experiments, administration of programmed cell death protein 1-binding antibody (anti-PD1 antibody) or epacadostat was concurrently initiated. Tumor size was determined by caliper measurements and comparative tumor growth suppression was assessed by longitudinal analyses of tumor growth data. For adoptive transfer, T cells from complete responder animals were isolated using paramagnetic beads and fluorescence-activated cell sorting.RESULTS: This study identifies mouse MHC class I-directed and II-directed, IDO1-derived peptides capable of eliciting antitumor responses, despite finding IDO1 expressed exclusively in tumor-infiltrating immune cells. Treatment of established tumors with anti-PD1 antibody and class I-directed but not class II-directed IDO1 peptide vaccines produced an enhanced antitumor response. Likewise, class I-directed and II-directed IDO1 peptides elicited an enhanced combinatorial response, suggesting distinct mechanisms of action. Consistent with this interpretation, adoptive transfer of isolated CD8+ T cells from class I and CD4+ T cells from class II peptide-vaccinated responder mice delayed tumor growth. The class II-directed response was completely IDO1-dependent while the class I-directed response included an IDO1-independent component consistent with antigen spread.CONCLUSIONS: The in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlight the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy.

KW - adaptive immunity

KW - immunotherapy

KW - indoleamine-pyrrole 2,3,-dioxygenase

KW - programmed cell death 1 receptor

KW - vaccination

UR - http://www.scopus.com/inward/record.url?scp=85088352086&partnerID=8YFLogxK

U2 - 10.1136/jitc-2020-000605

DO - 10.1136/jitc-2020-000605

M3 - Journal article

C2 - 32690770

VL - 8

JO - Journal for ImmunoTherapy of Cancer

JF - Journal for ImmunoTherapy of Cancer

SN - 2051-1426

IS - 2

M1 - 2020000605

ER -

ID: 61350228