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© Charles Dauguet
Virus VIH-2, second virus du sida isolé en 1985 par l'équipe du Pr. Montagnier de l'Institut Pasteur.
Publication : Molecular therapy. Methods & clinical development

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular therapy. Methods & clinical development - 26 Feb 2019

Delville M, Touzot F, Couzin C, Hmitou I, Djerroudi L, Ouedrani A, Lefrère F, Tuchman-Durand C, Mollet C, Fabreguettes JR, Ferry N, Laganier L, Magnani A, Magrin E, Jolaine V, Saez-Cirion A, Wolstein O, Symonds G, Frange P, Moins-Teisserenc H, Chaix-Baudier ML, Toubert A, Larghero J, Parquet N, Brignier AC, Barré-Sinoussi F, Oksenhendler E, Cavazzana M

Link to Pubmed [PMID] – 30911587

Mol Ther Methods Clin Dev 2019 Jun;13:303-309

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 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://www.ncbi.nlm.nih.gov/pubmed/30911587