Human immunodeficiency virus (HIV)-infected tumor xenografts as an in vivo model for antiviral therapy: role of alpha/beta interferon in restriction of tumor growth in nude mice injected with HIV-infected U937 tumor cells.
The host factors involved in the restriction of tumor growth were studied in nude mice transplanted with a cloned line of chronically human immunodeficiency virus (HIV)-infected U937 cells. HIV-infected and uninfected U937 cells exhibited the same growth patterns in culture. However, HIV-infected cells were not tumorigenic when injected subcutaneously in nude mice, whereas large solid tumors were observed in mice injected with uninfected U937 cells. Injection of nude mice with antibody to alpha/beta interferon (IFN-alpha/beta) enabled HIV-infected U937 cells to grow progressively in approximately 90 to 100% of mice. HIV-infected U937 cells formed solid tumors in the majority (60 to 90%) of either immunosuppressed (splenectomized, irradiated, and anti-asialo-GM1-treated) or genetically immunodeficient (bg/nu/xid) nude mice. In mice treated with antibodies to IFN-alpha/beta with established HIV-positive tumors, a direct correlation was found between p24 antigenemia and tumor size. Treatment of established HIV-positive U937 cell tumors with human IFN-alpha or mouse IFN-alpha/beta resulted in a clear-cut inhibition of both tumor growth and p24 HIV antigenemia. In contrast, treatment with tumor necrosis factor alpha markedly inhibited tumor growth but did not significantly decrease serum p24 levels. 3'-Azido-3'-deoxythymidine treatment did not affect either tumor growth or the levels of serum p24 antigen. These data indicate that endogenous IFN-alpha/beta is a crucial factor in the restriction of both tumor growth and p24 antigenemia in mice injected with HIV-infected tumor cells. Moreover, the results suggest that the development of HIV-1 p24 antigenemia in athymic immunosuppressed mice may represent an interesting in vivo model for anti-HIV therapy.
Puddu
P
P
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Locardi
C
C
Sestili
P
P
Varano
F
F
Petrini
C
C
Modesti
A
A
Masuelli
L
L
Gresser
I
I
Belardelli
F
F
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D015683:Gene Products, gag / Q000097:blood; D006678:HIV / Q000502:physiology* / Q000648:ultrastructure; D015488:HIV Antigens / Q000097:blood; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000276:immunology / Q000494:pharmacology*; D008223:Lymphoma; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014758:Viral Core Proteins / Q000097:blood; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000906:Antibodies; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D015215:Zidovudine