Intranuclear Relocalization of Matrix Binding Sites during T Cell Activation Detected by Amplified Fluorescence in Situ Hybridization

Methods ◽  
1999 ◽  
Vol 19 (3) ◽  
pp. 394-402 ◽  
Author(s):  
Shutao Cai ◽  
Terumi Kohwi-Shigematsu
Keyword(s):  
In Situ Hybridization ◽  
T Cell ◽  
Fluorescence In Situ Hybridization ◽  
T Cell Activation ◽  
Binding Sites ◽  
Cell Activation

scholarly journals Profiling T Cell Activation Using Single-Molecule Fluorescence In Situ Hybridization and Flow Cytometry

2014 ◽  
Vol 194 (2) ◽  
pp. 836-841 ◽  
Author(s):  
Yuri Bushkin ◽  
Felix Radford ◽  
Richard Pine ◽  
Alfred Lardizabal ◽  
Bonita T. Mangura ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
In Situ Hybridization ◽  
T Cell ◽  
Fluorescence In Situ Hybridization ◽  
T Cell Activation ◽  
Single Molecule ◽  
Cell Activation ◽  
Single Molecule Fluorescence

scholarly journals An Anti-CD2 Monoclonal Antibody That Both Inhibits and Stimulates T Cell Activation Recognizes a Subregion of CD2 Distinct from Known Ligand-Binding Sites

1993 ◽  
Vol 150 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Karen F. Kozarsky ◽  
Carlene Tsai ◽  
Cynthia M. Bott ◽  
Gopal Allada ◽  
Lan Lan Li ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Ligand Binding ◽  
T Cell Activation ◽  
Binding Sites ◽  
Cell Activation ◽  
Ligand Binding Sites

scholarly journals Impairment of T-Cell Activation in Head and Neck Cancer In Situ and In Vitro

1999 ◽  
Vol 125 (1) ◽  
pp. 82 ◽  
Author(s):  
Stephan Lang ◽  
Theresa L. Whiteside ◽  
Annette Lebeau ◽  
Reinhard Zeidler ◽  
Brigitte Mack ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
T Cell ◽  
Head And Neck ◽  
T Cell Activation ◽  
Neck Cancer ◽  
Cell Activation

Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9135-TPS9135
Author(s):  
Aaron Elliott Lisberg ◽  
Bin Liu ◽  
Ramin Salehi-Rad ◽  
Jay M. Lee ◽  
Linh Tran ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
T Cell Activation ◽  
Cell Activation ◽  
Phase I Trial ◽  
Primary Objective ◽  
Wild Type ◽  
T Cell Infiltration

TPS9135 Background: Effective immunotherapy options are lacking for patients with advanced non-small cell lung cancer (NSCLC) who progress on a programmed cell death-(ligand)1 [PD-(L)1] inhibitor and for those that are epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement positive after progression on tyrosine kinase inhibitor (TKI) therapy. One potential approach to improve immune checkpoint efficacy in these patient populations is to promote cytolytic T cell infiltration into tumors. This can be accomplished via in situ vaccination with functional antigen presenting cells (APCs) which can take advantage of the full repertoire of tumor antigens and convert the tumor into a lymph node-like environment promoting both local and systemic T cell activation. The chemokine CCL21 promotes co-localization of naive T cells and antigen-experienced dendritic cells (DCs) to facilitate T cell activation. Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in systemic antitumor immunity. However, increased PD-L1 expression was observed in some patient tumors, suggesting that tumor-mediated impairment of T cell function may be forestalling a more robust CCL21-DC mediated antitumor response. Similarly, improved PD-(L)1 inhibitor efficacy may be possible with enhanced T cell infiltration and augmented APC function following IT CCL21-DC. Therefore, we are conducting a phase I trial, combining IT CCL21-DC with pembrolizumab in patients with advanced NSCLC that are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy. Methods: Phase I, dose-escalating, multi-cohort trial followed by dose expansion. Maximum of 24 patients (9-12 escalation + 12 expansion) with stage IV NSCLC will be evaluated who have tumors accessible for IT injection and are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy. Three IT injections of autologous CCL21-DC (days 0, 21, 42) will be concurrently administered with pembrolizumab, followed by q3wk pembrolizumab up to 1 year. Primary objective of dose escalation is safety and determination of maximum tolerated dose (MTD) of IT CCL21-DC (5x106, 1x107, or 3x107) when combined with pembrolizumab. Primary objective of dose expansion is objective response rate at MTD. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment. Clinical trial information: NCT03546361.

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