Abstract 2805: Cancer-specific T cell receptor isolation for cancer immunotherapy

Malignant cells may be recognized by T cells binding cell surface Class I HLA-peptide complexes presenting disease-associated epitopes. Many cancer patients generate CD8 cytotoxic T cell responses to tumor-associated antigens, however due to the low avidity of these T cells and cancer cells developi...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 2805
Main Authors: Weigand, Luise U., Paston, Samantha, Hibbert, Linda, Ryan, Ruth K., Baker, Debbie E., Simmons, Ruth A., Harper, Jane V., Dukes, Joseph D., Bossi, Giovanna, Grand, Francis, Hickman, Emma, Powlesland, Alex, Vuidepot, Annelise, Hassan, Namir J., Jakobsen, Bent K.
Format: Journal Article
Language:English
Published: 01-10-2014
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract Malignant cells may be recognized by T cells binding cell surface Class I HLA-peptide complexes presenting disease-associated epitopes. Many cancer patients generate CD8 cytotoxic T cell responses to tumor-associated antigens, however due to the low avidity of these T cells and cancer cells developing escape mechanisms for avoiding destruction by T cells, the immune system fails to clear tumors. To overcome these issues, we have engineered novel, bi-functional protein therapeutics termed ImmTACs (Immune Mobilising monoclonal TCR Against Cancer) which re-direct the immune system to target and destroy tumor cells with a high degree of potency and specificity. An ImmTAC comprises a high affinity ‘monoclonal’ T cell Receptor (mTCR) targeting a cancer-associated HLA-peptide complex, fused to an anti-CD3 scFv domain which activates an anti-tumor T cell response. In order to produce ImmTACs, we have developed an integrated in-house process leading to the isolation of TCRs specific for validated cancer epitopes. The critical steps in this process are: antigen selection, epitope identification, T cell cloning, TCR isolation and binding to soluble peptide:MHC on the BIAcore. We describe each of these steps in more detail and present data to illustrate the successful isolation of a number of TCRs specific for various tumor associated antigens such as prostate and cancer testis antigens leading from this procedure. Citation Format: Luise U. Weigand, Samantha Paston, Linda Hibbert, Ruth K. Ryan, Debbie E. Baker, Ruth A. Simmons, Jane V. Harper, Joseph D. Dukes, Giovanna Bossi, Francis Grand, Emma Hickman, Alex Powlesland, Annelise Vuidepot, Namir J. Hassan, Bent K. Jakobsen. Cancer-specific T cell receptor isolation for cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2805. doi:10.1158/1538-7445.AM2014-2805
AbstractList Malignant cells may be recognized by T cells binding cell surface Class I HLA-peptide complexes presenting disease-associated epitopes. Many cancer patients generate CD8 cytotoxic T cell responses to tumor-associated antigens, however due to the low avidity of these T cells and cancer cells developing escape mechanisms for avoiding destruction by T cells, the immune system fails to clear tumors. To overcome these issues, we have engineered novel, bi-functional protein therapeutics termed ImmTACs (Immune Mobilising monoclonal TCR Against Cancer) which re-direct the immune system to target and destroy tumor cells with a high degree of potency and specificity. An ImmTAC comprises a high affinity ‘monoclonal’ T cell Receptor (mTCR) targeting a cancer-associated HLA-peptide complex, fused to an anti-CD3 scFv domain which activates an anti-tumor T cell response. In order to produce ImmTACs, we have developed an integrated in-house process leading to the isolation of TCRs specific for validated cancer epitopes. The critical steps in this process are: antigen selection, epitope identification, T cell cloning, TCR isolation and binding to soluble peptide:MHC on the BIAcore. We describe each of these steps in more detail and present data to illustrate the successful isolation of a number of TCRs specific for various tumor associated antigens such as prostate and cancer testis antigens leading from this procedure. Citation Format: Luise U. Weigand, Samantha Paston, Linda Hibbert, Ruth K. Ryan, Debbie E. Baker, Ruth A. Simmons, Jane V. Harper, Joseph D. Dukes, Giovanna Bossi, Francis Grand, Emma Hickman, Alex Powlesland, Annelise Vuidepot, Namir J. Hassan, Bent K. Jakobsen. Cancer-specific T cell receptor isolation for cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2805. doi:10.1158/1538-7445.AM2014-2805
Author Hibbert, Linda
Ryan, Ruth K.
Grand, Francis
Powlesland, Alex
Harper, Jane V.
Hassan, Namir J.
Weigand, Luise U.
Simmons, Ruth A.
Baker, Debbie E.
Bossi, Giovanna
Jakobsen, Bent K.
Hickman, Emma
Vuidepot, Annelise
Paston, Samantha
Dukes, Joseph D.
Author_xml – sequence: 1
  givenname: Luise U.
  surname: Weigand
  fullname: Weigand, Luise U.
– sequence: 2
  givenname: Samantha
  surname: Paston
  fullname: Paston, Samantha
– sequence: 3
  givenname: Linda
  surname: Hibbert
  fullname: Hibbert, Linda
– sequence: 4
  givenname: Ruth K.
  surname: Ryan
  fullname: Ryan, Ruth K.
– sequence: 5
  givenname: Debbie E.
  surname: Baker
  fullname: Baker, Debbie E.
– sequence: 6
  givenname: Ruth A.
  surname: Simmons
  fullname: Simmons, Ruth A.
– sequence: 7
  givenname: Jane V.
  surname: Harper
  fullname: Harper, Jane V.
– sequence: 8
  givenname: Joseph D.
  surname: Dukes
  fullname: Dukes, Joseph D.
– sequence: 9
  givenname: Giovanna
  surname: Bossi
  fullname: Bossi, Giovanna
– sequence: 10
  givenname: Francis
  surname: Grand
  fullname: Grand, Francis
– sequence: 11
  givenname: Emma
  surname: Hickman
  fullname: Hickman, Emma
– sequence: 12
  givenname: Alex
  surname: Powlesland
  fullname: Powlesland, Alex
– sequence: 13
  givenname: Annelise
  surname: Vuidepot
  fullname: Vuidepot, Annelise
– sequence: 14
  givenname: Namir J.
  surname: Hassan
  fullname: Hassan, Namir J.
– sequence: 15
  givenname: Bent K.
  surname: Jakobsen
  fullname: Jakobsen, Bent K.
BookMark eNqdzs2KwjAUBeCLKFh_HkHIC8RJakOLuyIOs5nFgPsQwy1G2qTcxIVvP2YcfABXl3M5B74FTH3wCLCRYiulaj6k2jW8riq1bb9LISteNkJNoHj9p1AIIRquqrqcwyLG6yMqKVQBP-05JjI2sTzas4PxFonHEa3rnGUnZrHvGaHFMQViLobeJBc86x7J_rWZG4abD-mCZMb7Cmad6SOu_-8S1OfxdPjilkKMhJ0eyQ2G7loKnf06O3V26qdfZ8ru3d0vrptQVA
ContentType Journal Article
DBID AAYXX
CITATION
DOI 10.1158/1538-7445.AM2014-2805
DatabaseName CrossRef
DatabaseTitle CrossRef
DatabaseTitleList CrossRef
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1538-7445
EndPage 2805
ExternalDocumentID 10_1158_1538_7445_AM2014_2805
GroupedDBID ---
-ET
18M
29B
2WC
34G
39C
476
53G
5GY
5RE
5VS
6J9
AAYXX
ABOCM
ACGFO
ACIWK
ACPRK
ACSVP
ADBBV
ADCOW
ADNWM
AENEX
AFHIN
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
BAWUL
BTFSW
CITATION
CS3
DIK
DU5
EBS
EJD
F5P
FRP
GX1
H13
IH2
KQ8
L7B
LSO
OK1
P0W
P2P
PQQKQ
RCR
RHF
RHI
RNS
SJN
TR2
W2D
W8F
WH7
WOQ
YKV
YZZ
ID FETCH-crossref_primary_10_1158_1538_7445_AM2014_28053
ISSN 0008-5472
IngestDate Thu Nov 21 23:16:39 EST 2024
IsPeerReviewed true
IsScholarly true
Issue 19_Supplement
Language English
LinkModel OpenURL
MergedId FETCHMERGED-crossref_primary_10_1158_1538_7445_AM2014_28053
ParticipantIDs crossref_primary_10_1158_1538_7445_AM2014_2805
PublicationCentury 2000
PublicationDate 2014-10-01
PublicationDateYYYYMMDD 2014-10-01
PublicationDate_xml – month: 10
  year: 2014
  text: 2014-10-01
  day: 01
PublicationDecade 2010
PublicationTitle Cancer research (Chicago, Ill.)
PublicationYear 2014
SSID ssj0005105
Score 4.348688
Snippet Malignant cells may be recognized by T cells binding cell surface Class I HLA-peptide complexes presenting disease-associated epitopes. Many cancer patients...
SourceID crossref
SourceType Aggregation Database
StartPage 2805
Title Abstract 2805: Cancer-specific T cell receptor isolation for cancer immunotherapy
Volume 74
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://sdu.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1LT8JAEN4AJsaL8Rnf2YO3prWUrrTeCGIwiInSRG9NabdCgkh4HPz3zuxuuwWNkYOXBjbtsHS-zM7OfDNLyGUcXSd2DJ5b6qapid1NzL4fpWbi-KB934li0We23as_vnq3LbdVKmWnYuqxf9U0jIGusXJ2DW3nQmEAPoPO4Qpah-uf9N7oY_AinhuOZzPc7zdRr1MTSyqRFmQEBgbrDbB0fDJHNjrMRzMOY3G3McSyEVWctZT4ldIM1SNoIJLAks0hrM1oZBViCy98-KaIkw-L4Qw8XEunrGaKuN-L3kG7g3x5aA_7fVVItBQweP5UKavFfGB0rGK4ourmxDdtgj2TufK8Hotrq1t3ZV_JzCzLw3sy-PmhOOVU04GUvfVsVli7s6_f1wWGtQ7571iNrpibfrzYh3tlfcxZi2K_xLwQxYQoJpRiQhRTJhsO2Dqxq7_vaJaRYtFm_1oVkYGYqx9nU3CPCn5OsEO21QaFNiSydkmJj_fIZldRMPbJUwYwioJu6Aq8aEARXjSDF83hRQFeVMKLLsHrgLC7VtBsm9mUwolsgRL--ipqh6Qy_hjzI0Ix0csTP2VpNXKTxI4cHkVJ6jLwQmPu1o6JtZ7sk3UfOCVbGoZnpDKfLvg5Kc-SxYXQ1BcK4W26
link.rule.ids 315,782,786,27933,27934
linkProvider Flying Publisher
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Abstract+2805%3A+Cancer-specific+T+cell+receptor+isolation+for+cancer+immunotherapy&rft.jtitle=Cancer+research+%28Chicago%2C+Ill.%29&rft.au=Weigand%2C+Luise+U.&rft.au=Paston%2C+Samantha&rft.au=Hibbert%2C+Linda&rft.au=Ryan%2C+Ruth+K.&rft.date=2014-10-01&rft.issn=0008-5472&rft.eissn=1538-7445&rft.volume=74&rft.issue=19_Supplement&rft.spage=2805&rft.epage=2805&rft_id=info:doi/10.1158%2F1538-7445.AM2014-2805&rft.externalDBID=n%2Fa&rft.externalDocID=10_1158_1538_7445_AM2014_2805
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0008-5472&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0008-5472&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0008-5472&client=summon