The world leader in serving science For Research Use Only. Not for use in diagnostic procedures. Geoffrey M. Lowman, PhD Senior Staff Scientist EACR - 02 July 2018 Evidence for antigen-driven TCRchain convergence in the tumor infiltrating T cell repertoire
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Evidence for antigen-driven TCR𝜷chain convergence …...Evidence for antigen-driven TCR 𝜷chain convergence in the tumor infiltrating T cell repertoire 2 For Research Use Only.
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The world leader in serving scienceFor Research Use Only. Not for use in diagnostic procedures.
Geoffrey M. Lowman, PhDSenior Staff Scientist EACR - 02 July 2018
Evidence for antigen-driven TCR𝜷 chain convergence in the tumor infiltrating T cell repertoire
2 For Research Use Only. Not for use in diagnostic procedures.
Conflicts
The authors are full-time employees of ThermoFisher Scientific
3 For Research Use Only. Not for use in diagnostic procedures.
Need for Biomarkers in Immuno-Oncology
• Biomarkers for prediction of adverse events during immunotherapy
• Biomarkers for prediction of response/non-response
Adapted from Sharma et al. Cell, 2015;161(2):205 with permission from Elsevier
Combination immunecheckpoint therapy
Combination Immunotherapy
PD-1 or CTLA-4
TumorDendritic
Cell
Macrophage
T cell
Checkpoint blockade may
target PD-1 and CTLA-4
pathways to upregulate
T cell cytotoxic response
Adapted from Ott, et al. Clin Cancer Res. 2013;19(19):5300
with permission from AACR.
4 For Research Use Only. Not for use in diagnostic procedures.
Need for Biomarkers in Immuno-Oncology
• Biomarkers for prediction of adverse events during immunotherapy
• Biomarkers for prediction of response/non-response
Adapted from Sharma et al. Cell, 2015;161(2):205 with permission from Elsevier
Combination immunecheckpoint therapy
Combination Immunotherapy
PD-1 or CTLA-4
TumorDendritic
Cell
Macrophage
T cell
Checkpoint blockade may
target PD-1 and CTLA-4
pathways to upregulate
T cell cytotoxic response
Adapted from Ott, et al. Clin Cancer Res. 2013;19(19):5300
with permission from AACR.
5 For Research Use Only. Not for use in diagnostic procedures.
Constant Leader FR1 FR2
Diversity (D) Joining (J)Variable (V)
CDR3
FR3
CDR1 CDR2
Sequencing Beta
Chain of T Cell
Receptors to
Characterize
Immune Status
AmpliSeq Primers ~330-340 bp
Long Read NGS assay capturing all 3
CDRs (1,2 &3). Uniquely captures
germline TRBV polymorphism from
blood/tissue to investigate
predisposition to adverse events.
Flexible input/sequencing depth
requirements covering samples with
low, medium, and high clonal
diversity.
Superior informatics for accurate
clonality and β chain sequence
assessment without interference from
primer bias.
10ng-
1mg
Ion Torrent Oncomine™ TCR Beta – LR Assay
Allelic variants may alter interaction of CDR1 and 2 with HLA
V-gene polymorphism Clonality / TCR convergence
TCRComplex.png used under creative commons license