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Next Article 
Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 785-793
PLENARY PAPER
Prolonged survival and tissue trafficking following adoptive
transfer of CD4 gene-modified autologous CD4+ and
CD8+ T cells in human immunodeficiency virus-infected
subjects
Ronald T. Mitsuyasu,
Peter A. Anton,
Steven G. Deeks,
David T. Scadden,
Elizabeth Connick,
Matthew T. Downs,
Andreas Bakker,
Margo R. Roberts,
Carl H. June,
Sayeh Jalali,
Andy A. Lin,
Rukmini Pennathur-Das, and
Kristen M. Hege
From the University of California, Los Angeles, CA; San Francisco
General Hospital, San Francisco, CA; Massachusetts General Hospital,
Boston, MA; University of Colorado Health Science Center, Denver, CO;
Statistics Collaborative, Washington DC; Specialty Labs, Los Angeles,
CA; University of Virginia, Charlottesville, VA; University of
Pennsylvania, Philadelphia, PA; and Cell Genesys, Inc, Foster City,
CA.
We have genetically engineered CD4+ and
CD8+ T cells with human immunodeficiency virus (HIV)
specificity by inserting a gene, CD4 , containing the extracellular
domain of human CD4 (which binds HIV env) linked to the zeta
() chain of the T-cell receptor (which mediates T-cell activation).
Twenty-four HIV-positive subjects received a single infusion of 2 to
3 × 1010 autologous CD4-modified CD4+
and CD8+ T cells administered with (n = 11) or
without (n = 13) interleukin-2 (IL-2). Subjects had CD4 counts
greater than 50/µL and viral loads of at least 1000 copies/mL at
entry. T cells were costimulated ex vivo through CD3 and CD28 and
expanded for approximately 2 weeks. CD4 was detected in 1% to 3%
of blood mononuclear cells at 8 weeks and 0.1% at 1 year after
infusion, and survival was not enhanced by IL-2. Trafficking of
gene-modified T cells to bulk rectal tissue and/or isolated lamina
propria lymphocytes was documented in a subset of 5 of 5 patients at 14 days and 2 of 3 at 1 year. A greater than 0.5 log mean decrease in
rectal tissue-associated HIV RNA was observed for at least 14 days,
suggesting compartmental antiviral activity of CD4 T cells.
CD4+ counts increased by 73/µL at 8 weeks in the group
receiving IL-2. There was no significant mean change in plasma HIV RNA
or blood proviral DNA in either treatment arm. This sustained,
high-level persistence of gene-modified T cells demonstrates the
feasibility of ex vivo T-cell gene therapy in HIV-infected adults and
suggests the importance of providing HIV-specific T-helper function.
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