scholarly journals Interleukin-4 Receptor Expression on AIDS-Associated Kaposi’s Sarcoma Cells and Their Targeting by a Chimeric Protein Comprised of Circularly Permuted Interleukin-4 and Pseudomonas Exotoxin

1997 ◽  
Vol 3 (5) ◽  
pp. 327-338 ◽  
Author(s):  
Syed R. Husain ◽  
Parkash Gill ◽  
Robert J. Kreitman ◽  
Ira Pastan ◽  
Raj K. Puri
10.1038/10541 ◽  
1999 ◽  
Vol 5 (7) ◽  
pp. 817-822 ◽  
Author(s):  
Syed R. Husain ◽  
Robert J. Kreitman ◽  
Ira Pastan ◽  
Raj K. Puri

2021 ◽  
Author(s):  
Simona Lupinacci ◽  
Anna Perri ◽  
Giuseppina Toteda ◽  
Donatella Vizza ◽  
Danilo Lofaro ◽  
...  

Science ◽  
1992 ◽  
Vol 255 (5050) ◽  
pp. 1430-1432 ◽  
Author(s):  
B. Nair ◽  
A. DeVico ◽  
S Nakamura ◽  
T. Copeland ◽  
Y Chen ◽  
...  

2000 ◽  
Vol 6 (1) ◽  
pp. 10-17 ◽  
Author(s):  
Chiara Marchisone ◽  
Federica Del Grosso ◽  
Luciana Masiello ◽  
Maria Prat ◽  
Leonardo Santi ◽  
...  

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 1852-1857 ◽  
Author(s):  
Karin Tarte ◽  
Sonja J. Olsen ◽  
Zhao Yang Lu ◽  
Eric Legouffe ◽  
Jean-François Rossi ◽  
...  

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.


2003 ◽  
Vol 279 (6) ◽  
pp. 4136-4143 ◽  
Author(s):  
Stefano Buttiglieri ◽  
Maria Chiara Deregibus ◽  
Stefania Bravo ◽  
Paola Cassoni ◽  
Roberto Chiarle ◽  
...  

Chemotherapy ◽  
2002 ◽  
Vol 48 (5) ◽  
pp. 238-243 ◽  
Author(s):  
Angela Hong ◽  
Bryan R. Leigh

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3707-3713 ◽  
Author(s):  
Mariko Kawakami ◽  
Koji Kawakami ◽  
Mitomu Kioi ◽  
Pamela Leland ◽  
Raj K. Puri

AbstractHodgkin lymphoma represents unique clinicopathologic features because Hodgkin and Reed-Sternberg (H-RS) cells produce a variety of cytokines, express a variety of cytokine receptors, and are surrounded by numerous nonmalignant immunoreactive cells. We found that receptors for interleukin-4 (IL-4R) are highly expressed in H-RS cells. To target interleukin-4 receptor (IL-4R), we used a recombinant protein fusing circularly permuted human IL-4 and Pseudomonas exotoxin termed IL438-37-PE38KDEL, or IL-4 cytotoxin. The cytotoxic effect of IL-4 cytotoxin on H-RS cell lines was determined to be moderate to high in vitro. We developed an infiltrating model of Hodgkin disease (HD) by injecting an adherent population of HD-MyZ cells subcutaneously into the flanks of beige/nude/X-linked immunodeficient mice. The animal model exhibited spontaneous metastasis of H-RS cells to lymph nodes and dissemination to vital organs, including the lungs. Intraperitoneal or intratumoral treatment of these mice with IL-4 cytotoxin resulted in regression of the primary tumor mass and a decrease in the incidence of lymph node metastasis. Mice injected with HD-MyZ cells demonstrated 203% prolonged survival (mean survival, 63 days) compared with control (mean survival, 31 days) when they received systemic IL-4 cytotoxin treatment. Because numerous H-RS cell lines express receptors for IL-4, IL-4 cytotoxin may be a unique agent for the treatment of Hodgkin lymphoma.


2010 ◽  
Vol 84 (21) ◽  
pp. 11134-11144 ◽  
Author(s):  
Qiliang Cai ◽  
Subhash C. Verma ◽  
Ji-Young Choi ◽  
Michelle Ma ◽  
Erle S. Robertson

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.


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