Molecular Therapy: Methods & Clinical Development (Jun 2019)
Safety of CD34+ Hematopoietic Stem Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma
- 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
Affiliations
- Marianne Delville
- Paris Descartes, Sorbonne Paris Cité, France; Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France; Laboratoire de Lymphohématopoïèse Humaine, INSERM U1163, Paris Descartes, Sorbonne Paris Cité, France; Corresponding author: Marianne Delville, Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France.
- Fabien Touzot
- Paris Descartes, Sorbonne Paris Cité, France; Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Chloé Couzin
- Paris Descartes, Sorbonne Paris Cité, France; Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Isabelle Hmitou
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Lounes Djerroudi
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Amani Ouedrani
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- François Lefrère
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Caroline Tuchman-Durand
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Chloé Mollet
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Jean-Roch Fabreguettes
- Département Essais Cliniques, AGEPS, Assistance Publique des Hôpitaux de Paris, Paris, France
- Nicolas Ferry
- Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Laurent Laganier
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Alessandra Magnani
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Elisa Magrin
- Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Valérie Jolaine
- Paris Descartes Necker – Cochin Clinical Research Unit, Assistance Publique-Hôpitaux de Paris, Paris, France
- Asier Saez-Cirion
- Unité HIV Inflammation et Persistance, Institut Pasteur, Paris, France
- Orit Wolstein
- CSL Behring, LLC (formerly Calimmune, Inc.), Darlinghurst, NSW, Australia
- Geoffrey Symonds
- CSL Behring, LLC (formerly Calimmune, Inc.), Darlinghurst, NSW, Australia
- Pierre Frange
- EHU 7328, Institut Imagine, Université Paris Descartes, Sorbonne Paris Cité, France; Unité d’Immunologie, d’Hématologie et de Rhumatologie Pédiatriques, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France
- Hélène Moins-Teisserenc
- INSERM U1160, Université Paris Diderot and Département d’Immunologie, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Marie-Laure Chaix-Baudier
- INSERM U944, Université Paris Diderot and Laboratoire de Virology Hôpital Saint-Louis, Paris, France
- Antoine Toubert
- INSERM U1160, Université Paris Diderot and Département d’Immunologie, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Jérôme Larghero
- CIC de Biothérapie CBT501, Université Paris Diderot and Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Nathalie Parquet
- Département d’Aphérèse Thérapeutique, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Anne C. Brignier
- Département d’Aphérèse Thérapeutique, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Françoise Barré-Sinoussi
- Département des Affaires Internationales, Institut Pasteur, Paris, France
- Eric Oksenhendler
- Université Paris Diderot and Service d’Immunopathologie Clinique, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- Marina Cavazzana
- Paris Descartes, Sorbonne Paris Cité, France; Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France; Laboratoire de Lymphohématopoïèse Humaine, INSERM U1163, Paris Descartes, Sorbonne Paris Cité, France
- Journal volume & issue
-
Vol. 13
pp. 303 – 309
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.
