Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Zinal S Chheda; Gary Kohanbash; Kaori Okada; Naznin Jahan; John Sidney; Matteo Pecoraro; Xinbo Yang; Diego A Carrera; Kira M Downey; Shruti Shrivastav; Shuming Liu; Yi Lin; Chetana Lagisetti; Pavlina Chuntova; Payal B Watchmaker; Sabine Mueller; Ian F Pollack; Raja Rajalingam; Angel M Carcaboso; Matthias Mann; Alessandro Sette; K Christopher Garcia; Yafei Hou; Hideho Okada

doi:10.1084/jem.20171046

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Zinal S Chheda, Gary Kohanbash, Kaori Okada, Naznin Jahan, John Sidney, Matteo Pecoraro, Xinbo Yang, Diego A Carrera, Kira M Downey, Shruti Shrivastav, Shuming Liu, Yi Lin, Chetana Lagisetti, Pavlina Chuntova, Payal B Watchmaker, Sabine Mueller, Ian F Pollack, Raja Rajalingam, Angel M Carcaboso, Matthias MannAlessandro Sette, K Christopher Garcia, Yafei Hou, Hideho Okada

88 Citationer (Scopus)

Abstract

The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector. TCR-transduced HLA-A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly suppressed the progression of glioma xenografts in mice. Alanine-scanning assays suggested the absence of known human proteins sharing the key amino acid residues required for recognition by the TCR, suggesting that the TCR could be safely used in patients. These data provide us with a strong basis for developing T cell-based therapy targeting this shared neoepitope.

Originalsprog	Engelsk
Tidsskrift	The Journal of Experimental Medicine
Vol/bind	215
Udgave nummer	1
Sider (fra-til)	141-157
Antal sider	17
ISSN	0022-1007
DOI	https://doi.org/10.1084/jem.20171046
Status	Udgivet - 1 jan. 2018
Udgivet eksternt	Ja

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10.1084/jem.20171046

jem_20171046.pdfForlagets udgivne version, 1,57 MBLicens: CC BY-NC-SA

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Chheda, Z. S., Kohanbash, G., Okada, K., Jahan, N., Sidney, J., Pecoraro, M., Yang, X., Carrera, D. A., Downey, K. M., Shrivastav, S., Liu, S., Lin, Y., Lagisetti, C., Chuntova, P., Watchmaker, P. B., Mueller, S., Pollack, I. F., Rajalingam, R., Carcaboso, A. M., ... Okada, H. (2018). Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy. The Journal of Experimental Medicine, 215(1), 141-157. https://doi.org/10.1084/jem.20171046

Chheda, ZS, Kohanbash, G, Okada, K, Jahan, N, Sidney, J, Pecoraro, M, Yang, X, Carrera, DA, Downey, KM, Shrivastav, S, Liu, S, Lin, Y, Lagisetti, C, Chuntova, P, Watchmaker, PB, Mueller, S, Pollack, IF, Rajalingam, R, Carcaboso, AM, Mann, M, Sette, A, Garcia, KC, Hou, Y & Okada, H 2018, 'Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy', The Journal of Experimental Medicine, bind 215, nr. 1, s. 141-157. https://doi.org/10.1084/jem.20171046

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abstract = "The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector. TCR-transduced HLA-A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly suppressed the progression of glioma xenografts in mice. Alanine-scanning assays suggested the absence of known human proteins sharing the key amino acid residues required for recognition by the TCR, suggesting that the TCR could be safely used in patients. These data provide us with a strong basis for developing T cell-based therapy targeting this shared neoepitope.",

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AU - Okada, Kaori

AU - Jahan, Naznin

AU - Sidney, John

AU - Pecoraro, Matteo

AU - Yang, Xinbo

AU - Carrera, Diego A

AU - Downey, Kira M

AU - Shrivastav, Shruti

AU - Liu, Shuming

AU - Lin, Yi

AU - Lagisetti, Chetana

AU - Chuntova, Pavlina

AU - Watchmaker, Payal B

AU - Mueller, Sabine

AU - Pollack, Ian F

AU - Rajalingam, Raja

AU - Carcaboso, Angel M

AU - Mann, Matthias

AU - Sette, Alessandro

AU - Garcia, K Christopher

AU - Hou, Yafei

AU - Okada, Hideho

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N2 - The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector. TCR-transduced HLA-A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly suppressed the progression of glioma xenografts in mice. Alanine-scanning assays suggested the absence of known human proteins sharing the key amino acid residues required for recognition by the TCR, suggesting that the TCR could be safely used in patients. These data provide us with a strong basis for developing T cell-based therapy targeting this shared neoepitope.

AB - The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector. TCR-transduced HLA-A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly suppressed the progression of glioma xenografts in mice. Alanine-scanning assays suggested the absence of known human proteins sharing the key amino acid residues required for recognition by the TCR, suggesting that the TCR could be safely used in patients. These data provide us with a strong basis for developing T cell-based therapy targeting this shared neoepitope.

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Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy

Abstract

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