scholarly journals Abstract 34: A high-content imaging platform for quantitative assessment of immunogenic tumor cell killing and T-cell proliferation in 3D tumoroids of fresh patient tumor samples

2019 ◽  
Author(s):  
Melanie Mediavilla-Varela ◽  
Vijayendra Agrawal ◽  
Melba Marie Page ◽  
Jenny Kreahling ◽  
Soner Altiok
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Tumor Cell ◽  
Quantitative Assessment ◽  
Cell Killing ◽  
T Cell Proliferation ◽  
High Content Imaging ◽  
Immunogenic Tumor ◽  
Immunogenic Tumor Cell ◽  
Tumor Cell Killing

Therapeutically Active RIG-I Agonist Induces Immunogenic Tumor Cell Killing in Breast Cancers

2018 ◽  
Vol 78 (21) ◽  
pp. 6183-6195 ◽  
Author(s):  
David L. Elion ◽  
Max E. Jacobson ◽  
Donna J. Hicks ◽  
Bushra Rahman ◽  
Violeta Sanchez ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Killing ◽  
Breast Cancers ◽  
Immunogenic Tumor ◽  
Immunogenic Tumor Cell ◽  
Tumor Cell Killing

scholarly journals T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4334-4342 ◽  
Author(s):  
Qi Zhou ◽  
Irene C. Schneider ◽  
Inan Edes ◽  
Annemarie Honegger ◽  
Patricia Bach ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gene Transfer ◽  
Tumor Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cell Killing ◽  
Specific Gene ◽  
Cd8 Cells ◽  
Tumor Cell Killing

AbstractTransfer of tumor-specific T-cell receptor (TCR) genes into patient T cells is a promising strategy in cancer immunotherapy. We describe here a novel vector (CD8-LV) derived from lentivirus, which delivers genes exclusively and specifically to CD8+ cells. CD8-LV mediated stable in vitro and in vivo reporter gene transfer as well as efficient transfer of genes encoding TCRs recognizing the melanoma antigen tyrosinase. Strikingly, T cells genetically modified with CD8-LV killed melanoma cells reproducibly more efficiently than CD8+ cells transduced with a conventional lentiviral vector. Neither TCR expression levels, nor the rate of activation-induced death of transduced cells differed between both vector types. Instead, CD8-LV transduced cells showed increased granzyme B and perforin levels as well as an up-regulation of CD8 surface expression in a small subpopulation of cells. Thus, a possible mechanism for CD8-LV enhanced tumor cell killing may be based on activation of the effector functions of CD8+ T cells by the vector particle displaying OKT8-derived CD8-scFv and an increase of the surface density of CD8, which functions as coreceptor for tumor-cell recognition. CD8-LV represents a powerful novel vector for TCR gene therapy and other applications in immunotherapy and basic research requiring CD8+ cell-specific gene delivery.

scholarly journals LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells

2019 ◽  
Vol 203 (4) ◽  
pp. 1076-1087 ◽  
Author(s):  
Aeryon Kim ◽  
Chia-Jung Han ◽  
Ian Driver ◽  
Aleksandra Olow ◽  
Andrew K. Sewell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cell ◽  
Cd8 T Cells ◽  
Cell Killing ◽  
Tumor Cell Killing ◽  
Bispecific T Cell Engager

scholarly journals Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data

2019 ◽  
Author(s):  
Prativa Sahoo ◽  
Xin Yang ◽  
Daniel Abler ◽  
Davide Maestrini ◽  
Vikram Adhikarla ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cell Therapy ◽  
Cell Killing ◽  
T Cell Proliferation ◽  
Tumor Growth Rate ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

AbstractChimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of hematological cancers and is currently being investigated for solid tumors including high-grade glioma brain tumors. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumors. In this work we use a mathematical model of predator-prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor t-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, CAR T-cell proliferation and exhaustion, and CAR T-cell persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyzer to parameterize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted as compared to higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumor growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumor characteristics including tumor growth rate and antigen level to maximize therapeutic benefit.Statement of SignificanceWe utilize a mathematical model to deconvolute the nonlinear contributions of CAR T-cell proliferation and exhaustion to predict therapeutic efficacy and dependence on CAR T-cell dose and target antigen levels.

scholarly journals Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0183390 ◽  
Author(s):  
Sandra L. Ross ◽  
Marika Sherman ◽  
Patricia L. McElroy ◽  
Julie A. Lofgren ◽  
Gordon Moody ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cell ◽  
Cell Killing ◽  
Tumor Cell Killing ◽  
Bispecific T Cell Engager

scholarly journals Correction: LILRB1 Blockade Enhances Bispecific T Cell Engager Antibody–Induced Tumor Cell Killing by Effector CD8+ T Cells

2019 ◽  
Vol 203 (7) ◽  
pp. 2023-2024
Author(s):  
Aeryon Kim ◽  
Chia-Jung Han ◽  
Ian Driver ◽  
Aleksandra Olow ◽  
Andrew K. Sewell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cell ◽  
Cd8 T Cells ◽  
Cell Killing ◽  
Tumor Cell Killing ◽  
Bispecific T Cell Engager
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