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Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases

INTRODUCTION: Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor modified T cell (CAR-T) hepatic artery infusions (HAI) for unresectable CEA+ liver metastases (LM). High neutrophil:lymphocyte ratios (NLR) predict poor outcome in cancer patien...

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Autores principales: Saied, Abdul, Licata, Lauren, Burga, Rachel A., Thorn, Mitchell, McCormack, Elise, Stainken, Brian F., Assanah, Earle O., Khare, Pranay D., Davies, Robin, Espat, N. Joseph, Junghans, Richard P., Katz, Steven C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245365/
https://www.ncbi.nlm.nih.gov/pubmed/25277132
http://dx.doi.org/10.1038/cgt.2014.50
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author Saied, Abdul
Licata, Lauren
Burga, Rachel A.
Thorn, Mitchell
McCormack, Elise
Stainken, Brian F.
Assanah, Earle O.
Khare, Pranay D.
Davies, Robin
Espat, N. Joseph
Junghans, Richard P.
Katz, Steven C.
author_facet Saied, Abdul
Licata, Lauren
Burga, Rachel A.
Thorn, Mitchell
McCormack, Elise
Stainken, Brian F.
Assanah, Earle O.
Khare, Pranay D.
Davies, Robin
Espat, N. Joseph
Junghans, Richard P.
Katz, Steven C.
author_sort Saied, Abdul
collection PubMed
description INTRODUCTION: Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor modified T cell (CAR-T) hepatic artery infusions (HAI) for unresectable CEA+ liver metastases (LM). High neutrophil:lymphocyte ratios (NLR) predict poor outcome in cancer patients and we hypothesized that NLR changes would correlate with early responses to CAR-T HAI. METHODS: Six patients completed the protocol. Three patients received CAR-T HAI in dose escalation (1 × 10(8), 1 × 10(9), and 1 × 10(10)cells) and the remainder received 3 doses (1 × 10(10) cells) with IL2 support. Serum cytokines and NLR were measured at multiple time points. RESULTS: The mean NLR for all patients was 13.9 (range 4.8-38.1). NLR increased in four patients following treatment with a mean fold change of 1.9. Serum IL6 levels and NLR fold-changes demonstrated a trend towards a positive correlation (r=0.77, p=0.10). Patients with poor CEA responses were significantly more likely to have higher NLR level increases (p=0.048). CONCLUSIONS: Increased NLR levels were associated with poor responses following CAR-T HAI. NLR variations and associated cytokine changes may be useful surrogates of response to CAR-T HAI.
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spelling pubmed-42453652015-05-01 Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases Saied, Abdul Licata, Lauren Burga, Rachel A. Thorn, Mitchell McCormack, Elise Stainken, Brian F. Assanah, Earle O. Khare, Pranay D. Davies, Robin Espat, N. Joseph Junghans, Richard P. Katz, Steven C. Cancer Gene Ther Article INTRODUCTION: Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor modified T cell (CAR-T) hepatic artery infusions (HAI) for unresectable CEA+ liver metastases (LM). High neutrophil:lymphocyte ratios (NLR) predict poor outcome in cancer patients and we hypothesized that NLR changes would correlate with early responses to CAR-T HAI. METHODS: Six patients completed the protocol. Three patients received CAR-T HAI in dose escalation (1 × 10(8), 1 × 10(9), and 1 × 10(10)cells) and the remainder received 3 doses (1 × 10(10) cells) with IL2 support. Serum cytokines and NLR were measured at multiple time points. RESULTS: The mean NLR for all patients was 13.9 (range 4.8-38.1). NLR increased in four patients following treatment with a mean fold change of 1.9. Serum IL6 levels and NLR fold-changes demonstrated a trend towards a positive correlation (r=0.77, p=0.10). Patients with poor CEA responses were significantly more likely to have higher NLR level increases (p=0.048). CONCLUSIONS: Increased NLR levels were associated with poor responses following CAR-T HAI. NLR variations and associated cytokine changes may be useful surrogates of response to CAR-T HAI. 2014-10-03 2014-11 /pmc/articles/PMC4245365/ /pubmed/25277132 http://dx.doi.org/10.1038/cgt.2014.50 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Saied, Abdul
Licata, Lauren
Burga, Rachel A.
Thorn, Mitchell
McCormack, Elise
Stainken, Brian F.
Assanah, Earle O.
Khare, Pranay D.
Davies, Robin
Espat, N. Joseph
Junghans, Richard P.
Katz, Steven C.
Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases
title Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases
title_full Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases
title_fullStr Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases
title_full_unstemmed Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases
title_short Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified T cell infusions for liver metastases
title_sort neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor modified t cell infusions for liver metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245365/
https://www.ncbi.nlm.nih.gov/pubmed/25277132
http://dx.doi.org/10.1038/cgt.2014.50
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