Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy
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Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy. / Chheda, Zinal S; Kohanbash, Gary; Okada, Kaori; Jahan, Naznin; Sidney, John; Pecoraro, Matteo; Yang, Xinbo; Carrera, Diego A; Downey, Kira M; Shrivastav, Shruti; Liu, Shuming; Lin, Yi; Lagisetti, Chetana; Chuntova, Pavlina; Watchmaker, Payal B; Mueller, Sabine; Pollack, Ian F; Rajalingam, Raja; Carcaboso, Angel M; Mann, Matthias; Sette, Alessandro; Garcia, K Christopher; Hou, Yafei; Okada, Hideho.
In: The Journal of Experimental Medicine, Vol. 215, No. 1, 01.2018, p. 141-157.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy
AU - Chheda, Zinal S
AU - Kohanbash, Gary
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
N1 - © 2018 Chheda et al.
PY - 2018/1
Y1 - 2018/1
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.
KW - Journal Article
U2 - 10.1084/jem.20171046
DO - 10.1084/jem.20171046
M3 - Journal article
C2 - 29203539
VL - 215
SP - 141
EP - 157
JO - The Journal of Experimental Medicine
JF - The Journal of Experimental Medicine
SN - 0022-1007
IS - 1
ER -
ID: 186869209