3Département de Biothérapie [CHU Necker] (Groupe Hospitalier Necker-Enfants Malades
Localisation du service : Carré Necker porte N5, 1er étage
149 rue de Sèvres 75743 Paris Cedex 15 - France)
7CIC 1419 - CIC - Mère Enfant Necker Cochin Paris Centre (Site Hôpital Cochin: 89, rue d'Assas- 75006 PARIS
Site Hôpital Necker: 149 rue de Sèvres- 75743 Paris cedex 15
Site Hôpital Sainte Anne: 1 rue Cabanis- 75014 Paris
Site Maternité Port Royal: 53 avenue de l'observatoire- 75014 PARIS - France)
Abstract : 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.
https://hal-pasteur.archives-ouvertes.fr/pasteur-02549969 Contributor : Asier Saez-CirionConnect in order to contact the contributor Submitted on : Tuesday, April 21, 2020 - 7:05:34 PM Last modification on : Friday, May 6, 2022 - 10:10:04 AM