Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft model

10.1038/10541 ◽  
1999 ◽  
Vol 5 (7) ◽  
pp. 817-822 ◽  
Author(s):  
Syed R. Husain ◽  
Robert J. Kreitman ◽  
Ira Pastan ◽  
Raj K. Puri
Keyword(s):  
Kaposi's Sarcoma ◽  
Xenograft Model ◽  
Kaposi’S Sarcoma ◽  
Interleukin 4 ◽  
Interleukin 4 Receptor

scholarly journals Clinical-Grade Functional Dendritic Cells From Patients With Multiple Myeloma Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 1852-1857 ◽  
Author(s):  
Karin Tarte ◽  
Sonja J. Olsen ◽  
Zhao Yang Lu ◽  
Eric Legouffe ◽  
Jean-François Rossi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Kaposi's Sarcoma ◽  
Fluorescein Isothiocyanate ◽  
Kaposi’S Sarcoma ◽  
Interleukin 4 ◽  
Clinical Grade ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Abstract Bone marrow dendritic cells (DC) from patients with multiple myeloma (MM) were recently reported to be infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Because immunotherapy strategies using DC are very promising in this disease, we looked for KSHV DNA in clinical-grade DC generated in vitro from MM patients. Adherent apheresis cells from MM patients were maintained for 7 days in clinical-grade X-VIVO 15 culture medium supplemented with granulocyte-macrophage colony-stimulating factor, interleukin-4, or interleukin-13. Tumor necrosis factor α was added for the last 2 days. We obtained a cell population with a DC phenotype able to endocytose fluorescein isothiocyanate (FITC)-dextran and efficiently activate resting allogenic T lymphocytes. To detect KSHV DNA, we used polymerase chain reaction (PCR) followed by Southern blotting of PCR product with a sensitivity detecting a few copies of viral DNA. All the PCR were repeated in a blinded fashion three times, on 1 μg and 0.2 μg of genomic DNA, in two different laboratories. Clinical-grade DC from 10 (91%) of 11 patients were not infected with KSHV. The apheresis cells and the purified CD34+ cells from the same patients were also negative. A very weak PCR band was detected with DC from one patient, but the initial apheresis cells were negative. The detection of KSHV infection in 1 (9%) of 11 MM patients probably represents background seroprevalence. It seems likely that functional and clinical-grade DC from MM patients can safely be used in clinical trials.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Inhibits Interleukin-4-Mediated STAT6 Phosphorylation To Regulate Apoptosis and Maintain Latency

2010 ◽  
Vol 84 (21) ◽  
pp. 11134-11144 ◽  
Author(s):  
Qiliang Cai ◽  
Subhash C. Verma ◽  
Ji-Young Choi ◽  
Michelle Ma ◽  
Erle S. Robertson
Keyword(s):  
Immune Response ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Cellular Growth ◽  
Interleukin 4 ◽  
Nuclear Antigen ◽  
Viral Agent ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Cytokine-mediated JAK/STAT signaling controls numerous important biologic responses like immune function, cellular growth, and differentiation. Inappropriate activation of this signaling pathway is associated with a range of malignancies. Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious viral agent associated with Kaposi's sarcoma and may also contribute to B-cell disorders, which include primary effusion lymphoma (PEL) and multicentric Castleman's disease. However, regulation of cytokine-mediated lymphocytic immune response by KSHV is not fully understood. In this report, we demonstrate that KSHV suppresses the interleukin-4 (IL-4)-stimulated immune response of B-lymphocyte activation and cell proliferation. Moreover, we show that the latency-associated nuclear antigen (LANA) encoded by KSHV is essential for viral blocking of IL-4-induced signaling. LANA reduces phosphorylation of the signal transducers and activators of transcription 6 (STAT6) on Y-641 and concomitantly its DNA binding ability. Importantly, knockdown of endogenous STAT6 dramatically increases the sensitivity of PEL cells to low-serum stress or chemical-mediated cellular apoptosis and reactivation of KSHV from latent replication. Thus, these findings suggest that the IL-4/STAT6 signaling network is precisely controlled by KSHV for survival, maintenance of latency, and suppression of the host cytokine immune response of the virus-infected cells.

scholarly journals Interleukin-4 in the treatment of AIDS-related Kaposi’s sarcoma

1997 ◽  
Vol 8 (1) ◽  
pp. 79-83 ◽  
Author(s):  
A. Tulpule ◽  
B. Joshi ◽  
N. DeGuzman ◽  
B.M. Espina ◽  
R. Mocharnuk ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Interleukin 4

scholarly journals Clinical-Grade Functional Dendritic Cells From Patients With Multiple Myeloma Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 1852-1857 ◽  
Author(s):  
Karin Tarte ◽  
Sonja J. Olsen ◽  
Zhao Yang Lu ◽  
Eric Legouffe ◽  
Jean-François Rossi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Kaposi's Sarcoma ◽  
Fluorescein Isothiocyanate ◽  
Kaposi’S Sarcoma ◽  
Interleukin 4 ◽  
Clinical Grade ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Bone marrow dendritic cells (DC) from patients with multiple myeloma (MM) were recently reported to be infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Because immunotherapy strategies using DC are very promising in this disease, we looked for KSHV DNA in clinical-grade DC generated in vitro from MM patients. Adherent apheresis cells from MM patients were maintained for 7 days in clinical-grade X-VIVO 15 culture medium supplemented with granulocyte-macrophage colony-stimulating factor, interleukin-4, or interleukin-13. Tumor necrosis factor α was added for the last 2 days. We obtained a cell population with a DC phenotype able to endocytose fluorescein isothiocyanate (FITC)-dextran and efficiently activate resting allogenic T lymphocytes. To detect KSHV DNA, we used polymerase chain reaction (PCR) followed by Southern blotting of PCR product with a sensitivity detecting a few copies of viral DNA. All the PCR were repeated in a blinded fashion three times, on 1 μg and 0.2 μg of genomic DNA, in two different laboratories. Clinical-grade DC from 10 (91%) of 11 patients were not infected with KSHV. The apheresis cells and the purified CD34+ cells from the same patients were also negative. A very weak PCR band was detected with DC from one patient, but the initial apheresis cells were negative. The detection of KSHV infection in 1 (9%) of 11 MM patients probably represents background seroprevalence. It seems likely that functional and clinical-grade DC from MM patients can safely be used in clinical trials.

scholarly journals Desferrioxamine enhances aids-associated Kaposi's sarcoma tumor development in a xenograft model

2002 ◽  
Vol 100 (2) ◽  
pp. 140-143 ◽  
Author(s):  
Thierry Simonart ◽  
Johan R. Boelaert ◽  
Graciela Andrei ◽  
Joost J. van den Oord ◽  
Chantale Degraef ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Tumor Development ◽  
Xenograft Model ◽  
Kaposi’S Sarcoma

Lack of Antitumor Activity and Intolerance of Interleukin-4 in Patients with Advanced HIV Disease and Kaposi's Sarcoma

2002 ◽  
Vol 22 (11) ◽  
pp. 1143-1148 ◽  
Author(s):  
Steven A. Miles ◽  
Marcia Testa ◽  
Jie Huang ◽  
Michael Wade ◽  
Judy Carden ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Interleukin 4 ◽  
Hiv Disease ◽  
Advanced Hiv Disease
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