Gene Transfer for HIV Using Autologous T Cells

Summary

This is a pilot study to determine the safety and feasibility of lentivirus-transduced T-cell immunotherapy in patients who have failed highly active anti-retrovirus therapy (HAART).

Timeline

Start

2010-04

Primary completion

2011-01

Completion

2011-01

Publications

• Background Levine BL, Bernstein WB, Aronson NE, Schlienger K, Cotte J, Perfetto S, Humphries MJ, Ratto-Kim S, Birx DL, Steffens C, Landay A, Carroll RG, June CH. Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection. Nat Med. 2002 Jan;8(1):47-53. doi: 10.1038/nm0102-47.
• Background Sarver N, Cantin EM, Chang PS, Zaia JA, Ladne PA, Stephens DA, Rossi JJ. Ribozymes as potential anti-HIV-1 therapeutic agents. Science. 1990 Mar 9;247(4947):1222-5. doi: 10.1126/science.2107573.
• Background Bai J, Gorantla S, Banda N, Cagnon L, Rossi J, Akkina R. Characterization of anti-CCR5 ribozyme-transduced CD34+ hematopoietic progenitor cells in vitro and in a SCID-hu mouse model in vivo. Mol Ther. 2000 Mar;1(3):244-54. doi: 10.1006/mthe.2000.0038.
• Background Bauer G, Valdez P, Kearns K, Bahner I, Wen SF, Zaia JA, Kohn DB. Inhibition of human immunodeficiency virus-1 (HIV-1) replication after transduction of granulocyte colony-stimulating factor-mobilized CD34+ cells from HIV-1-infected donors using retroviral vectors containing anti-HIV-1 genes. Blood. 1997 Apr 1;89(7):2259-67.
• Background Lee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, Salvaterra P, Rossi J. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol. 2002 May;20(5):500-5. doi: 10.1038/nbt0502-500.
• Background Li MJ, Bauer G, Michienzi A, Yee JK, Lee NS, Kim J, Li S, Castanotto D, Zaia J, Rossi JJ. Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. Mol Ther. 2003 Aug;8(2):196-206. doi: 10.1016/s1525-0016(03)00165-5.
• Background Li MJ, Kim J, Li S, Zaia J, Yee JK, Anderson J, Akkina R, Rossi JJ. Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther. 2005 Nov;12(5):900-9. doi: 10.1016/j.ymthe.2005.07.524. Epub 2005 Aug 22.

Drugs

Indications