PMID- 29661776
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20200502
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 24
IP  - 14
DP  - 2018 Jul 15
TI  - Targeting the Leukemia Antigen PR1 with Immunotherapy for the Treatment of 
      Multiple Myeloma.
PG  - 3386-3396
LID - 10.1158/1078-0432.CCR-17-2626 [doi]
AB  - Purpose: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from 
      neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 
      is cross-presented by solid tumors, leukemia, and antigen-presenting cells, 
      including B cells. We have also shown that cross-presentation of PR1 by solid 
      tumors renders them susceptible to killing by PR1-targeting immunotherapies. As 
      multiple myeloma is derived from B cells, we investigated whether multiple 
      myeloma is also capable of PR1 cross-presentation and subsequently capable of 
      being targeted by using PR1 immunotherapies.Experimental Design: We tested 
      whether multiple myeloma is capable of cross-presenting PR1 and subsequently 
      becomes susceptible to PR1-targeting immunotherapies, using multiple myeloma cell 
      lines, a xenograft mouse model, and primary multiple myeloma patient 
      samples.Results: Here we show that multiple myeloma cells lack endogenous NE and 
      P3, are able to take up exogenous NE and P3, and cross-present PR1 on HLA-A2. 
      Cross-presentation by multiple myeloma utilizes the conventional antigen 
      processing machinery, including the proteasome and Golgi, and is not affected by 
      immunomodulating drugs (IMiD). Following PR1 cross-presentation, we are able to 
      target multiple myeloma with PR1-CTL and anti-PR1/HLA-A2 antibody both in vitro 
      and in vivoConclusions: Collectively, our data demonstrate that PR1 is a novel 
      tumor-associated antigen target in multiple myeloma and that multiple myeloma is 
      susceptible to immunotherapies that target cross-presented antigens. Clin Cancer 
      Res; 24(14); 3386-96. (c)2018 AACR.
CI  - (c)2018 American Association for Cancer Research.
FAU - Alatrash, Gheath
AU  - Alatrash G
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas. galatras@mdanderson.org jmolldre@mdanderson.org.
FAU - Perakis, Alexander A
AU  - Perakis AA
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Kerros, Celine
AU  - Kerros C
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Peters, Haley L
AU  - Peters HL
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Sukhumalchandra, Pariya
AU  - Sukhumalchandra P
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Zhang, Mao
AU  - Zhang M
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Jakher, Haroon
AU  - Jakher H
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Zope, Madhushree
AU  - Zope M
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Patenia, Rebecca
AU  - Patenia R
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Sergeeva, Anna
AU  - Sergeeva A
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Yi, Shuhua
AU  - Yi S
AD  - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Young, Ken H
AU  - Young KH
AD  - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Philips, Anne V
AU  - Philips AV
AD  - Department of Breast Surgical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Cernosek, Amanda M
AU  - Cernosek AM
AUID- ORCID: 0000-0002-3912-5068
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Garber, Haven R
AU  - Garber HR
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Qiao, Na
AU  - Qiao N
AD  - Department of Breast Surgical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Weng, Jinsheng
AU  - Weng J
AD  - Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, Texas.
FAU - St John, Lisa S
AU  - St John LS
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Lu, Sijie
AU  - Lu S
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Clise-Dwyer, Karen
AU  - Clise-Dwyer K
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Mittendorf, Elizabeth A
AU  - Mittendorf EA
AD  - Department of Breast Surgical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Ma, Qing
AU  - Ma Q
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Molldrem, Jeffrey J
AU  - Molldrem JJ
AUID- ORCID: 0000-0003-1196-1715
AD  - Department of Stem Cell Transplantation and Cellular Therapy, Section of 
      Transplant Immunology, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas. galatras@mdanderson.org jmolldre@mdanderson.org.
LA  - eng
GR  - P50 CA142509/CA/NCI NIH HHS/United States
GR  - T32 CA009598/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180416
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Immunologic Factors)
RN  - 0 (Peptide Fragments)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/drug effects/immunology
MH  - Antigen-Presenting Cells/immunology
MH  - Antineoplastic Agents, Immunological/*pharmacology
MH  - Biological Transport
MH  - Cell Line, Tumor
MH  - Complement Activation
MH  - Cross-Priming/drug effects/immunology
MH  - Cytotoxicity, Immunologic
MH  - Disease Models, Animal
MH  - HLA-A2 Antigen/chemistry/*immunology/metabolism
MH  - Humans
MH  - Immunologic Factors/pharmacology
MH  - Immunomodulation/drug effects
MH  - Mice
MH  - Multiple Myeloma/drug therapy/*immunology/metabolism/pathology
MH  - Peptide Fragments/*antagonists & inhibitors/*immunology
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2018/04/18 06:00
MHDA- 2019/12/21 06:00
CRDT- 2018/04/18 06:00
PHST- 2017/09/11 00:00 [received]
PHST- 2018/02/19 00:00 [revised]
PHST- 2018/04/10 00:00 [accepted]
PHST- 2018/04/18 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2018/04/18 06:00 [entrez]
AID - 1078-0432.CCR-17-2626 [pii]
AID - 10.1158/1078-0432.CCR-17-2626 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2018 Jul 15;24(14):3386-3396. doi: 
      10.1158/1078-0432.CCR-17-2626. Epub 2018 Apr 16.