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: 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
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2021
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/125725
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id I19-R120-10915-125725
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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