HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy
Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunother...
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Autores principales: | , , , , , , , , , , , , , |
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Formato: | Articulo Preprint |
Lenguaje: | Inglés |
Publicado: |
2021
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Materias: | |
Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/125725 |
Aporte de: |
id |
I19-R120-10915-125725 |
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record_format |
dspace |
institution |
Universidad Nacional de La Plata |
institution_str |
I-19 |
repository_str |
R-120 |
collection |
SEDICI (UNLP) |
language |
Inglés |
topic |
Biología Immunology Immunotherapy Cancer immunotherapy Hla-g antigens Hla-g gene Biology |
spellingShingle |
Biología Immunology Immunotherapy Cancer immunotherapy Hla-g antigens Hla-g gene Biology Palma, María Belén Tronik-Le Roux, Diana Amin, Guadalupe Castañeda, Sheila Möbbs, Alan Miqueas Scarafía, María Agustina La Greca, Alejandro Daouya, Marina Poras, Isabelle Inda, Ana María Moro, Lucía Natalia Carosella, Edgardo D. García, Marcela Nilda Miriuka, Santiago Gabriel HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy |
topic_facet |
Biología Immunology Immunotherapy Cancer immunotherapy Hla-g antigens Hla-g gene Biology |
description |
Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them.
Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial. In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLAG was reached to different degrees, including complete silencing. Most importantly, HLA-G – cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer. |
format |
Articulo Preprint |
author |
Palma, María Belén Tronik-Le Roux, Diana Amin, Guadalupe Castañeda, Sheila Möbbs, Alan Miqueas Scarafía, María Agustina La Greca, Alejandro Daouya, Marina Poras, Isabelle Inda, Ana María Moro, Lucía Natalia Carosella, Edgardo D. García, Marcela Nilda Miriuka, Santiago Gabriel |
author_facet |
Palma, María Belén Tronik-Le Roux, Diana Amin, Guadalupe Castañeda, Sheila Möbbs, Alan Miqueas Scarafía, María Agustina La Greca, Alejandro Daouya, Marina Poras, Isabelle Inda, Ana María Moro, Lucía Natalia Carosella, Edgardo D. García, Marcela Nilda Miriuka, Santiago Gabriel |
author_sort |
Palma, María Belén |
title |
HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy |
title_short |
HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy |
title_full |
HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy |
title_fullStr |
HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy |
title_full_unstemmed |
HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy |
title_sort |
hla-g gene editing: a novel therapeutic alternative in cancer immunotherapy |
publishDate |
2021 |
url |
http://sedici.unlp.edu.ar/handle/10915/125725 |
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