PMID- 30911587 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2329-0501 (Print) IS - 2329-0501 (Electronic) IS - 2329-0501 (Linking) VI - 13 DP - 2019 Jun 14 TI - Safety of CD34(+) Hematopoietic Stem Cells and CD4(+) T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma. PG - 303-309 LID - 10.1016/j.omtm.2019.02.006 [doi] AB - 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. FAU - Delville, Marianne AU - Delville M AD - Paris Descartes, Sorbonne Paris Cite, France. AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. AD - Laboratoire de Lymphohematopoiese Humaine, INSERM U1163, Paris Descartes, Sorbonne Paris Cite, France. FAU - Touzot, Fabien AU - Touzot F AD - Paris Descartes, Sorbonne Paris Cite, France. AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Couzin, Chloe AU - Couzin C AD - Paris Descartes, Sorbonne Paris Cite, France. AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Hmitou, Isabelle AU - Hmitou I AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Djerroudi, Lounes AU - Djerroudi L AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Ouedrani, Amani AU - Ouedrani A AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Lefrere, Francois AU - Lefrere F AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Tuchman-Durand, Caroline AU - Tuchman-Durand C AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Mollet, Chloe AU - Mollet C AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Fabreguettes, Jean-Roch AU - Fabreguettes JR AD - Departement Essais Cliniques, AGEPS, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Ferry, Nicolas AU - Ferry N AD - Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Laganier, Laurent AU - Laganier L AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Magnani, Alessandra AU - Magnani A AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Magrin, Elisa AU - Magrin E AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Jolaine, Valerie AU - Jolaine V AD - Paris Descartes Necker - Cochin Clinical Research Unit, Assistance Publique-Hopitaux de Paris, Paris, France. FAU - Saez-Cirion, Asier AU - Saez-Cirion A AD - Unite HIV Inflammation et Persistance, Institut Pasteur, Paris, France. FAU - Wolstein, Orit AU - Wolstein O AD - CSL Behring, LLC (formerly Calimmune, Inc.), Darlinghurst, NSW, Australia. FAU - Symonds, Geoffrey AU - Symonds G AD - CSL Behring, LLC (formerly Calimmune, Inc.), Darlinghurst, NSW, Australia. FAU - Frange, Pierre AU - Frange P AD - EHU 7328, Institut Imagine, Universite Paris Descartes, Sorbonne Paris Cite, France. AD - Unite d'Immunologie, d'Hematologie et de Rhumatologie Pediatriques, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Moins-Teisserenc, Helene AU - Moins-Teisserenc H AD - INSERM U1160, Universite Paris Diderot and Departement d'Immunologie, Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Chaix-Baudier, Marie-Laure AU - Chaix-Baudier ML AD - INSERM U944, Universite Paris Diderot and Laboratoire de Virology Hopital Saint-Louis, Paris, France. FAU - Toubert, Antoine AU - Toubert A AD - INSERM U1160, Universite Paris Diderot and Departement d'Immunologie, Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Larghero, Jerome AU - Larghero J AD - CIC de Biotherapie CBT501, Universite Paris Diderot and Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Parquet, Nathalie AU - Parquet N AD - Departement d'Apherese Therapeutique, Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Brignier, Anne C AU - Brignier AC AD - Departement d'Apherese Therapeutique, Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Barre-Sinoussi, Francoise AU - Barre-Sinoussi F AD - Departement des Affaires Internationales, Institut Pasteur, Paris, France. FAU - Oksenhendler, Eric AU - Oksenhendler E AD - Universite Paris Diderot and Service d'Immunopathologie Clinique, Hopital Saint Louis, Assistance Publique des Hopitaux de Paris, Paris, France. FAU - Cavazzana, Marina AU - Cavazzana M AD - Paris Descartes, Sorbonne Paris Cite, France. AD - Clinical Investigation Center CIC1416 and Departement de Biotherapie, Hopital Necker, Assistance Publique des Hopitaux de Paris, Paris, France. AD - Laboratoire de Lymphohematopoiese Humaine, INSERM U1163, Paris Descartes, Sorbonne Paris Cite, France. LA - eng PT - Journal Article DEP - 20190226 PL - United States TA - Mol Ther Methods Clin Dev JT - Molecular therapy. Methods & clinical development JID - 101624857 PMC - PMC6416524 EDAT- 2019/03/27 06:00 MHDA- 2019/03/27 06:01 PMCR- 2019/02/26 CRDT- 2019/03/27 06:00 PHST- 2018/09/18 00:00 [received] PHST- 2019/02/20 00:00 [accepted] PHST- 2019/03/27 06:00 [entrez] PHST- 2019/03/27 06:00 [pubmed] PHST- 2019/03/27 06:01 [medline] PHST- 2019/02/26 00:00 [pmc-release] AID - S2329-0501(19)30023-3 [pii] AID - 10.1016/j.omtm.2019.02.006 [doi] PST - epublish SO - Mol Ther Methods Clin Dev. 2019 Feb 26;13:303-309. doi: 10.1016/j.omtm.2019.02.006. eCollection 2019 Jun 14.