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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.

Details

Title
Safety of CD34 + Hematopoietic Stem Cells and CD4 + T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma
Author
Delville, Marianne 1 ; Touzot, Fabien 2 ; Couzin, Chloé 2 ; Hmitou, Isabelle 3 ; Djerroudi, Lounes 3 ; Ouedrani, Amani 3 ; Lefrère, François 3 ; Tuchman-Durand, Caroline 3 ; Mollet, Chloé 3 ; Jean-Roch Fabreguettes 4 ; Ferry, Nicolas 5 ; Laganier, Laurent 3 ; Magnani, Alessandra 3 ; Magrin, Elisa 3 ; Jolaine, Valérie 6 ; Saez-Cirion, Asier 7 ; Wolstein, Orit 8 ; Symonds, Geoffrey 8 ; Frange, Pierre 9 ; Moins-Teisserenc, Hélène 10 ; Chaix-Baudier, Marie-Laure 11 ; Toubert, Antoine 10 ; Larghero, Jérôme 12 ; Parquet, Nathalie 13 ; Brignier, Anne C 13 ; Barré-Sinoussi, Françoise 14 ; Oksenhendler, Eric 15 ; Cavazzana, Marina 1 

1  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 
2  Paris Descartes, Sorbonne Paris Cité, France; Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France 
3  Clinical Investigation Center CIC1416 and Département de Biothérapie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France 
4  Département Essais Cliniques, AGEPS, Assistance Publique des Hôpitaux de Paris, Paris, France 
5  Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France 
6  Paris Descartes Necker – Cochin Clinical Research Unit, Assistance Publique-Hôpitaux de Paris, Paris, France 
7  Unité HIV Inflammation et Persistance, Institut Pasteur, Paris, France 
8  CSL Behring, LLC (formerly Calimmune, Inc.), Darlinghurst, NSW, Australia 
9  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 
10  INSERM U1160, Université Paris Diderot and Département d’Immunologie, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France 
11  INSERM U944, Université Paris Diderot and Laboratoire de Virology Hôpital Saint-Louis, Paris, France 
12  CIC de Biothérapie CBT501, Université Paris Diderot and Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France 
13  Département d’Aphérèse Thérapeutique, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France 
14  Département des Affaires Internationales, Institut Pasteur, Paris, France 
15  Université Paris Diderot and Service d’Immunopathologie Clinique, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France 
Pages
303-309
Section
Protocol
Publication year
2019
Publication date
Jun 14, 2019
Publisher
Elsevier Limited
e-ISSN
23290501
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1016/j.omtm.2019.02.006
ProQuest document ID
2307589145
Copyright
©2019. The Authors