HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy
| Autor: | 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 |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Popis: | 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. Facultad de Ciencias Médicas Comisión de Investigaciones Científicas de la provincia de Buenos Aires |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|