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@ARTICLE{Grassl:284811,
author = {N. Grassl$^*$ and K. Sahm$^*$ and H. Süße and I.
Poschke$^*$ and L. Bunse$^*$ and T. Bunse$^*$ and T.
Boschert$^*$ and I. Mildenberger$^*$ and A.-K. Rupp and M.
P. Ewinger and L.-M. Lanz and M. Denk$^*$ and G. Tabatabai
and M. W. Ronellenfitsch and U. Herrlinger and M. Glas and
D. Krex and P. Vajkoczy and A. Wick and I. Harting and F.
Sahm$^*$ and A. von Deimling$^*$ and M. Bendszus and W. Wick
and M. Platten$^*$},
title = {{INTERCEPT} {H}3: a multicenter phase {I} peptide vaccine
trial for the treatment of {H}3-mutated diffuse midline
gliomas.},
journal = {Neurological research and practice},
volume = {5},
number = {1},
issn = {2524-3489},
address = {[London]},
publisher = {BioMed Central},
reportid = {DKFZ-2023-02110},
pages = {55},
year = {2023},
note = {#EA:D170#LA:D170# / HI-TRON},
abstract = {Diffuse midline gliomas (DMG) are universally lethal
central nervous system tumors that carry almost unanimously
the clonal driver mutation histone-3 K27M (H3K27M). The
single amino acid substitution of lysine to methionine
harbors a neoantigen that is presented in tumor tissue. The
long peptide vaccine H3K27M-vac targeting this major
histocompatibility complex class II (MHC class
II)-restricted neoantigen induces mutation-specific immune
responses that suppress the growth of H3K27M+ flank tumors
in an MHC-humanized rodent model.INTERCEPT H3 is a
non-controlled open label, single arm, multicenter national
phase 1 trial to assess safety, tolerability and
immunogenicity of H3K27M-vac in combination with standard
radiotherapy and the immune checkpoint inhibitor
atezolizumab (ATE). 15 adult patients with newly diagnosed
K27M-mutant histone-3.1 (H3.1K27M) or histone-3.3 (H3.3K27M)
DMG will be enrolled in this trial. The 27mer peptide
vaccine H3K27M-vac will be administered concomitantly to
standard radiotherapy (RT) followed by combinatorial
treatment with the programmed death-ligand 1 (PD-L1)
targeting antibody ATE. The first three vaccines will be
administered bi-weekly (q2w) followed by a dose at the
beginning of recovery after RT and six-weekly
administrations of doses 5 to 11 thereafter. In a safety
lead-in, the first three patients (pts. 1-3) will be
enrolled sequentially.H3K27M-vac is a neoepitope targeting
long peptide vaccine derived from the clonal driver mutation
H3K27M in DMG. The INTERCEPT H3 trial aims at demonstrating
(1) safety and (2) immunogenicity of repeated fixed dose
vaccinations of H3K27M-vac administered with RT and ATE in
adult patients with newly diagnosed H3K27M-mutant
DMG.NCT04808245.},
keywords = {Antigen (Other) / Atezolizumab (Other) / Central nervous
system tumor (Other) / Diffuse midline glioma (Other) /
Glioma (Other) / Immunotherapy (Other) / T cell (Other) /
Vaccine (Other)},
cin = {D170 / HD01 / TU01 / B300},
ddc = {610},
cid = {I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)TU01-20160331 / I:(DE-He78)B300-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37853454},
doi = {10.1186/s42466-023-00282-4},
url = {https://inrepo02.dkfz.de/record/284811},
}