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Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings

Various studies have emphasized an immunodepression state observed at the tumour site. To reverse this defect and based upon animal studies, we initiated a phase I clinical trial of gene therapy in which various doses of xenogeneic monkey fibroblasts (Vero cells) genetically engineered to produce hu...

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Autores principales: Tartour, E, Mehtali, M, Sastre-Garau, X, Joyeux, I, Mathiot, C, Pleau, J M, Squiban, P, Rochlitz, C, Courtney, M, Jantscheff, P, Herrmann, R, Pouillart, P, Fridman, W H, Dorval, T
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363414/
https://www.ncbi.nlm.nih.gov/pubmed/11076653
http://dx.doi.org/10.1054/bjoc.2000.1492
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author Tartour, E
Mehtali, M
Sastre-Garau, X
Joyeux, I
Mathiot, C
Pleau, J M
Squiban, P
Rochlitz, C
Courtney, M
Jantscheff, P
Herrmann, R
Pouillart, P
Fridman, W H
Dorval, T
author_facet Tartour, E
Mehtali, M
Sastre-Garau, X
Joyeux, I
Mathiot, C
Pleau, J M
Squiban, P
Rochlitz, C
Courtney, M
Jantscheff, P
Herrmann, R
Pouillart, P
Fridman, W H
Dorval, T
author_sort Tartour, E
collection PubMed
description Various studies have emphasized an immunodepression state observed at the tumour site. To reverse this defect and based upon animal studies, we initiated a phase I clinical trial of gene therapy in which various doses of xenogeneic monkey fibroblasts (Vero cells) genetically engineered to produce human IL-2 were administered intratumorally in 8 patients with metastatic solid tumours. No severe adverse effect was observed in the 8 patients analysed during this clinical trial even in the highest dose (5 ¥ 107 cells) group. This absence of toxicity seems to be associated with rapid elimination of Vero-IL-2 cells from the organism. Indeed, exogenous IL-2 mRNA could no longer be detected in the peripheral whole blood 48 hours after Vero-IL-2 cell administration. In addition, we did not find any expression of exogenous IL-2 mRNA in post-therapeutic lesions removed 29 days after the start of therapy. A major finding of this trial concerns the two histological responses of two treated subcutaneous nodules not associated with an apparent clinical response. The relationship between local treatment and tumour regression was supported by replacement of tumour cells by inflammatory cells in regressing lesions and marked induction of T and natural killer cell derived cytokines (IL-2, IL-4, IFNg …) in post-therapeutic lesions analysed 28 days after the start of Vero-IL-2 administration. Gene therapy using xenogeneic cells as vehicle may therefore present certain advantages over other vectors, such as its complete absence of toxicity. Furthermore, the in vivo biological effect of immunostimulatory genes, i.e IL-2-, may be potentiated by the xenogeneic rejection reaction. © 2000 Cancer Research Campaign http://www.bjcancer.com
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spelling pubmed-23634142009-09-10 Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings Tartour, E Mehtali, M Sastre-Garau, X Joyeux, I Mathiot, C Pleau, J M Squiban, P Rochlitz, C Courtney, M Jantscheff, P Herrmann, R Pouillart, P Fridman, W H Dorval, T Br J Cancer Regular Article Various studies have emphasized an immunodepression state observed at the tumour site. To reverse this defect and based upon animal studies, we initiated a phase I clinical trial of gene therapy in which various doses of xenogeneic monkey fibroblasts (Vero cells) genetically engineered to produce human IL-2 were administered intratumorally in 8 patients with metastatic solid tumours. No severe adverse effect was observed in the 8 patients analysed during this clinical trial even in the highest dose (5 ¥ 107 cells) group. This absence of toxicity seems to be associated with rapid elimination of Vero-IL-2 cells from the organism. Indeed, exogenous IL-2 mRNA could no longer be detected in the peripheral whole blood 48 hours after Vero-IL-2 cell administration. In addition, we did not find any expression of exogenous IL-2 mRNA in post-therapeutic lesions removed 29 days after the start of therapy. A major finding of this trial concerns the two histological responses of two treated subcutaneous nodules not associated with an apparent clinical response. The relationship between local treatment and tumour regression was supported by replacement of tumour cells by inflammatory cells in regressing lesions and marked induction of T and natural killer cell derived cytokines (IL-2, IL-4, IFNg …) in post-therapeutic lesions analysed 28 days after the start of Vero-IL-2 administration. Gene therapy using xenogeneic cells as vehicle may therefore present certain advantages over other vectors, such as its complete absence of toxicity. Furthermore, the in vivo biological effect of immunostimulatory genes, i.e IL-2-, may be potentiated by the xenogeneic rejection reaction. © 2000 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2000-12 2000-11-22 /pmc/articles/PMC2363414/ /pubmed/11076653 http://dx.doi.org/10.1054/bjoc.2000.1492 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Tartour, E
Mehtali, M
Sastre-Garau, X
Joyeux, I
Mathiot, C
Pleau, J M
Squiban, P
Rochlitz, C
Courtney, M
Jantscheff, P
Herrmann, R
Pouillart, P
Fridman, W H
Dorval, T
Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
title Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
title_full Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
title_fullStr Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
title_full_unstemmed Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
title_short Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
title_sort phase i clinical trial with il-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363414/
https://www.ncbi.nlm.nih.gov/pubmed/11076653
http://dx.doi.org/10.1054/bjoc.2000.1492
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