| Autor: |
Marianne Delville, Fabien Touzot, Chloé Couzin, Isabelle Hmitou, Lounes Djerroudi, Amani Ouedrani, François Lefrère, Caroline Tuchman-Durand, Chloé Mollet, Jean-Roch Fabreguettes, Nicolas Ferry, Laurent Laganier, Alessandra Magnani, Elisa Magrin, Valérie Jolaine, Asier Saez-Cirion, Orit Wolstein, Geoffrey Symonds, Pierre Frange, Hélène Moins-Teisserenc, Marie-Laure Chaix-Baudier, Antoine Toubert, Jérôme Larghero, Nathalie Parquet, Anne C. Brignier, Françoise Barré-Sinoussi, Eric Oksenhendler, Marina Cavazzana |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 13, Iss , Pp 303-309 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2019.02.006 |
| Popis: |
Although the risk of developing lymphoma has decreased in the highly active antiretroviral therapy era, this cancer remains the major cause of mortality in HIV-infected patients. Autologous hematopoietic stem cell transplantation (ASCT) outcome does not differ for HIV-infected versus HIV-uninfected patients. We propose to develop a new treatment for HIV-associated high-risk lymphoma based on autologous transplantation of two genetically modified products: CD4+ T lymphocytes and CD34+ hematopoietic stem cells (HSPCs). The cells will be transduced ex vivo with the Cal-1 lentiviral vector encoding for both a short hairpin RNA (shRNA) against CCR5 (sh5) and the HIV-1 fusion inhibitor C46. The transduced cells will be resistant to HIV infection by two complementary mechanisms: impaired binding of the virus to the cellular CCR5 co-receptor and decreased fusion of the virus as C46 interacts with gp41 and inhibits HIV infection. This phase I/II pilot study, also entitled GENHIV, will involve two French participating centers: Saint Louis Hospital and Necker Hospital in Paris. We plan to enroll five HIV-1-infected patients presenting with high-risk lymphoma and require a treatment with ASCT. The primary objective of this study is to evaluate the safety, feasibility, and success of engraftment of Cal-1 gene-transduced CD4+ T lymphocytes and CD34+ HSPCs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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