Cytotoxic T-lymphocyte induction in asymptomatic HIV-1-infected patients immunized with Retrovector-transduced autologous fibroblasts expressing HIV-1IIIB Env/Rev proteins.
OBJECTIVE
To demonstrate the safety and enhancement of HIV-1-specific immune responses in HIV-infected asymptomatic patients following treatment with retroviral vector (Retrovector)-transduced autologous fibroblasts (VTAF) expressing HIV-1IIIB Env/Rev proteins.


METHODS
A non-placebo-controlled, single arm Phase I study.


METHODS
Four HIV-1-seropositive asymptomatic volunteers were selected based on age (18-50 years), CD4/CD3 lymphocyte counts (> 600 x 10(6)/l or > 40%), and positive delayed-type hypersensitivity test to at least one recall antigen.


METHODS
Patients were treated at 2-week intervals with a total of three intramuscular injections of irradiated autologous fibroblasts transduced with a molecularly engineered, non-replicating amphotropic murine retrovector encoding the HIV-1IIIB Env/Rev proteins.


METHODS
The clinical status of patients was assessed by history, physical examination, serum chemistry and hematology, CD4/CD3 lymphocyte counts, HIV viral burden, and monitored throughout the study to detect potentially treatment-induced toxic or unwanted side-effects. In addition, HIV-1-specific cytotoxic T-lymphocyte (CTL) activity was measured to determine the biological activity of VTAF.


RESULTS
No acute local or systemic adverse events occurred following three injections with VTAF. Furthermore, a statistically significant increase of CD8+ CTL activity against HIV-1IIIB Env/Rev-expressing targets was observed in peripheral blood mononuclear cells from two out of four patients.


CONCLUSIONS
This is the first report of the administration of a gene transfer treatment to HIV-1-infected patients and provides initial support for the safety and activity of retrovector-transduced fibroblasts administered to asymptomatic patients. This treatment resulted in the detection of increased HIV-1IIIB Env/Rev-specific CTL activity in two HIV-seropositive patients and could provide a better understanding of the role of CTL activity in HIV disease progression.
Ziegner
U H
UH
Viagene, Inc., San Diego, CA 92121
Peters
G
G
Jolly
D J
DJ
Mento
S J
SJ
Galpin
J
J
Prussak
C E
CE
Barber
J R
JR
Hartnett
D E
DE
Bohart
C
C
Klump
W
W
D016915:AIDS Vaccines / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000818:Animals; D017690:Cell Transplantation; D015686:Gene Products, env / Q000276:immunology*; D015694:Gene Products, rev / Q000276:immunology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006679:HIV Seropositivity / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic; D014182:Transplantation, Autologous / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015686:Gene Products, env; D015694:Gene Products, rev; D014614:Vaccines, Synthetic; D054321:rev Gene Products, Human Immunodeficiency Virus