PMID- 38416845
OWN - NLM
STAT- MEDLINE
DCOM- 20240301
LR  - 20240508
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 16
IP  - 736
DP  - 2024 Feb 28
TI  - A functional identification platform reveals frequent, spontaneous 
      neoantigen-specific T cell responses in patients with cancer.
PG  - eabj9905
LID - 10.1126/scitranslmed.abj9905 [doi]
AB  - The clinical impact of tumor-specific neoantigens as both immunotherapeutic 
      targets and biomarkers has been impeded by the lack of efficient methods for 
      their identification and validation from routine samples. We have developed a 
      platform that combines bioinformatic analysis of tumor exomes and transcriptional 
      data with functional testing of autologous peripheral blood mononuclear cells 
      (PBMCs) to simultaneously identify and validate neoantigens recognized by 
      naturally primed CD4(+) and CD8(+) T cell responses across a range of tumor types 
      and mutational burdens. The method features a human leukocyte antigen 
      (HLA)-agnostic bioinformatic algorithm that prioritizes mutations recognized by 
      patient PBMCs at a greater than 40% positive predictive value followed by a 
      short-term in vitro functional assay, which allows interrogation of 50 to 75 
      expressed mutations from a single 50-ml blood sample. Neoantigens validated by 
      this method include both driver and passenger mutations, and this method 
      identified neoantigens that would not have been otherwise detected using an in 
      silico prediction approach. These findings reveal an efficient approach to 
      systematically validate clinically actionable neoantigens and the T cell 
      receptors that recognize them and demonstrate that patients across a variety of 
      human cancers have a diverse repertoire of neoantigen-specific T cells.
FAU - Miller, Aaron M
AU  - Miller AM
AUID- ORCID: 0000-0001-9834-428X
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
AD  - Division of Hematology and Oncology, UCSD Moores Cancer Center, 3855 Health 
      Sciences Drive, La Jolla, CA 92093, USA.
FAU - Kosaloglu-Yalcin, Zeynep
AU  - Kosaloglu-Yalcin Z
AUID- ORCID: 0000-0003-0961-5055
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Westernberg, Luise
AU  - Westernberg L
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Montero, Leslie
AU  - Montero L
AUID- ORCID: 0009-0001-6101-3337
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Bahmanof, Milad
AU  - Bahmanof M
AUID- ORCID: 0000-0001-9264-1996
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Frentzen, Angela
AU  - Frentzen A
AUID- ORCID: 0000-0002-1193-6715
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Lanka, Manasa
AU  - Lanka M
AUID- ORCID: 0000-0003-3301-7768
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Logandha Ramamoorthy Premlal, Ashmitaa
AU  - Logandha Ramamoorthy Premlal A
AUID- ORCID: 0000-0001-7110-4235
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Seumois, Gregory
AU  - Seumois G
AUID- ORCID: 0000-0002-8164-6852
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Greenbaum, Jason
AU  - Greenbaum J
AUID- ORCID: 0000-0002-1381-0390
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Brightman, Spencer E
AU  - Brightman SE
AUID- ORCID: 0000-0002-9930-7218
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Soria Zavala, Karla
AU  - Soria Zavala K
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Thota, Rukman R
AU  - Thota RR
AUID- ORCID: 0000-0002-9225-9516
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Naradikian, Martin S
AU  - Naradikian MS
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
FAU - Makani, Samir S
AU  - Makani SS
AD  - Division of Hematology and Oncology, UCSD Moores Cancer Center, 3855 Health 
      Sciences Drive, La Jolla, CA 92093, USA.
FAU - Lippman, Scott M
AU  - Lippman SM
AUID- ORCID: 0000-0002-1643-4124
AD  - Division of Hematology and Oncology, UCSD Moores Cancer Center, 3855 Health 
      Sciences Drive, La Jolla, CA 92093, USA.
FAU - Sette, Alessandro
AU  - Sette A
AUID- ORCID: 0000-0001-7013-2250
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
FAU - Cohen, Ezra E W
AU  - Cohen EEW
AD  - Division of Hematology and Oncology, UCSD Moores Cancer Center, 3855 Health 
      Sciences Drive, La Jolla, CA 92093, USA.
FAU - Peters, Bjoern
AU  - Peters B
AUID- ORCID: 0000-0002-8457-6693
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
AD  - Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 
      92037, USA.
FAU - Schoenberger, Stephen P
AU  - Schoenberger SP
AUID- ORCID: 0000-0002-9870-7340
AD  - Center for Cancer Immunotherapy, La Jolla Institute for Immunology, 9420 Athena 
      Circle, La Jolla, CA 92037, USA.
AD  - Division of Hematology and Oncology, UCSD Moores Cancer Center, 3855 Health 
      Sciences Drive, La Jolla, CA 92093, USA.
LA  - eng
PT  - Journal Article
DEP - 20240228
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
EIN - Sci Transl Med. 2024 May 8;16(746):eadp8153. PMID: 38718137
MH  - Humans
MH  - *Antigens, Neoplasm/metabolism
MH  - *Neoplasms/genetics/metabolism
MH  - CD8-Positive T-Lymphocytes
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Lymphocytes, Tumor-Infiltrating
EDAT- 2024/02/28 18:42
MHDA- 2024/03/01 06:44
CRDT- 2024/02/28 14:04
PHST- 2024/03/01 06:44 [medline]
PHST- 2024/02/28 18:42 [pubmed]
PHST- 2024/02/28 14:04 [entrez]
AID - 10.1126/scitranslmed.abj9905 [doi]
PST - ppublish
SO  - Sci Transl Med. 2024 Feb 28;16(736):eabj9905. doi: 10.1126/scitranslmed.abj9905. 
      Epub 2024 Feb 28.