PMID- 31921218
OWN - NLM
STAT- MEDLINE
DCOM- 20201105
LR  - 20231027
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Neoantigens in Hematological Malignancies-Ultimate Targets for Immunotherapy?
PG  - 3004
LID - 10.3389/fimmu.2019.03004 [doi]
LID - 3004
AB  - Neoantigens derive from non-synonymous somatic mutations in malignant cells. 
      Recognition of neoantigens presented via human leukocyte antigen (HLA) molecules 
      on the tumor cell surface by T cells holds promise to enable highly specific and 
      effective anti-cancer immune responses and thus neoantigens provide an 
      exceptionally attractive target for immunotherapy. While genome sequencing 
      approaches already enable the reliable identification of somatic mutations in 
      tumor samples, the identification of mutation-derived, naturally HLA-presented 
      neoepitopes as targets for immunotherapy remains challenging, particularly in low 
      mutational burden cancer entities, including hematological malignancies. Several 
      approaches have been utilized to identify neoepitopes from primary tumor samples. 
      Besides whole genome sequencing with subsequent in silico prediction of potential 
      mutation-derived HLA ligands, mass spectrometry (MS) allows for the only unbiased 
      identification of naturally presented mutation-derived HLA ligands. The 
      feasibility of characterizing and targeting these novel antigens has recently 
      been demonstrated in acute myeloid leukemia (AML). Several immunogenic, 
      HLA-presented peptides derived from mutated Nucleophosmin 1 (NPM1) were 
      identified, allowing for the generation of T-cell receptor-transduced 
      NPM1(mut)-specific T cells with anti-leukemic activity in a xenograft mouse 
      model. Neoantigen-specific T-cell responses have also been identified for 
      peptides derived from mutated isocitrate dehydrogenase (IDH(mut)), and specific 
      T-cell responses could be induced by IDH(mut) peptide vaccination. In this 
      review, we give a comprehensive overview on known neoantigens in hematological 
      malignancies, present possible prediction and discovery tools and discuss their 
      role as targets for immunotherapy approaches.
CI  - Copyright (c) 2019 Roerden, Nelde and Walz.
FAU - Roerden, Malte
AU  - Roerden M
AD  - Department of Hematology, Oncology, Rheumatology and Clinical Immunology, 
      University Hospital Tubingen, Tubingen, Germany.
AD  - Department of Immunology, Institute for Cell Biology, University of Tubingen, 
      Tubingen, Germany.
FAU - Nelde, Annika
AU  - Nelde A
AD  - Department of Immunology, Institute for Cell Biology, University of Tubingen, 
      Tubingen, Germany.
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), University Hospital Tubingen, Tubingen, Germany.
FAU - Walz, Juliane S
AU  - Walz JS
AD  - Department of Hematology, Oncology, Rheumatology and Clinical Immunology, 
      University Hospital Tubingen, Tubingen, Germany.
AD  - Department of Immunology, Institute for Cell Biology, University of Tubingen, 
      Tubingen, Germany.
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), University Hospital Tubingen, Tubingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20191220
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA Antigens)
RN  - 0 (NPM1 protein, human)
RN  - 0 (Npm1 protein, mouse)
RN  - 0 (Peptides)
RN  - 117896-08-9 (Nucleophosmin)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens, Neoplasm/*immunology
MH  - HLA Antigens/immunology
MH  - *Hematologic Neoplasms/immunology/pathology/therapy
MH  - Humans
MH  - Immunotherapy/*instrumentation
MH  - *Leukemia, Myeloid, Acute/immunology/pathology/therapy
MH  - Mice
MH  - Nucleophosmin
MH  - Peptides/*immunology
MH  - *T-Lymphocytes/immunology/pathology
MH  - Xenograft Model Antitumor Assays
PMC - PMC6934135
OTO - NOTNLM
OT  - HLA antigens
OT  - NPM1 mutations
OT  - hematological malignancies
OT  - immunopeptidomics
OT  - mass spectrometry
OT  - neoantigens
EDAT- 2020/01/11 06:00
MHDA- 2020/11/06 06:00
PMCR- 2019/01/01
CRDT- 2020/01/11 06:00
PHST- 2019/09/28 00:00 [received]
PHST- 2019/12/06 00:00 [accepted]
PHST- 2020/01/11 06:00 [entrez]
PHST- 2020/01/11 06:00 [pubmed]
PHST- 2020/11/06 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.03004 [doi]
PST - epublish
SO  - Front Immunol. 2019 Dec 20;10:3004. doi: 10.3389/fimmu.2019.03004. eCollection 
      2019.