Safety of CD34+ Hematopoietic Stem Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma - Institut Pasteur Access content directly
Journal Articles Molecular Therapy - Methods and Clinical Development Year : 2019

Safety of CD34+ Hematopoietic Stem Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma

Nicolas Ferry
Orit Wolstein
  • Function : Author
Geoffrey Symonds
  • Function : Author
Nathalie Parquet
Eric Oksenhendler

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.
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pasteur-02549969 , version 1 (21-04-2020)

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Attribution - NonCommercial - NoDerivatives

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Marianne Delville, Fabien Touzot, Chloé Couzin, Isabelle Hmitou, Lounes Djerroudi, et al.. Safety of CD34+ Hematopoietic Stem Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma. Molecular Therapy - Methods and Clinical Development, 2019, 13, pp.303-309. ⟨10.1016/j.omtm.2019.02.006⟩. ⟨pasteur-02549969⟩
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