scholarly journals Induction of neutrophil FC-gamma receptor I expression can be used as a marker for biologic activity of recombinant interferon-gamma in vivo [letter]

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 2088-2090 ◽  
Author(s):  
TW Huizinga ◽  
CE Van der Schoot ◽  
D Roos ◽  
RS Weening
Keyword(s):  
Interferon Gamma ◽  
Fc Gamma Receptor ◽  
Recombinant Interferon ◽  
Gamma Receptor ◽  
Biologic Activity

In vivo biological response to recombinant interferon-gamma during a phase I dose-response trial in patients with metastatic melanoma.

1990 ◽  
Vol 8 (6) ◽  
pp. 1070-1082 ◽  
Author(s):  
J M Kirkwood ◽  
M S Ernstoff ◽  
T Trautman ◽  
G Hebert ◽  
Y Nishida ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Dose Response ◽  
Dose Range ◽  
Cell Subset ◽  
Optimal Dosage ◽  
Antitumor Effects ◽  
Ifn Gamma ◽  
Recombinant Interferon ◽  
Wide Range

Interferon-gamma (IFN gamma), as produced by recombinant DNA technology, has shown a wide range of immunomodulatory activity in vitro and in vivo. Clinical studies have attempted to establish a dose-response relationship to define optimal dosage ranges for induction of effector cell function and host response in patients with cancer. We conducted a randomized trial to test the in vivo biologic activity of five daily dosages ranging from 3 to 3,000 micrograms/m2, administered by daily 2-hour bolus injection or by continuous infusion for 14 days. We demonstrate comparable immunobiologic effects of recombinant IFN gamma (rIFN gamma; Biogen, Inc, Cambridge, MA) administered by these two schedules at the various dosages tested, and have defined a relationship of dose to biologic response over this 3-log10 dose range. Oligo 2'5' adenylate synthetase (2'5'As) induction, natural-killer (NK) cell activity, and T-cell subset distribution (heightened T helper/suppressor ratio) showed the most consistent treatment-associated changes and the greatest immunobiologic effects at dosages of 300 to 1,000 micrograms/m2. Mononuclear cell DR and DQ antigen expression showed no consistent dose-related treatment effect. The relevance of the phenotypic, functional, and enzymologic effects observed in this trial to any clinical antitumor effects of IFN gamma in cancer therapy must now be established.

scholarly journals Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular BacteriumFrancisella tularensisby the Inhibitory Receptor FcγRIIB

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Brian J. Franz ◽  
Ying Li ◽  
Constantine Bitsaktsis ◽  
Bibiana V. Iglesias ◽  
Giang Pham ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Immune Protection ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Significant Difference ◽  
Cytokine Levels ◽  
Iga Production ◽  
Protection Against Infection ◽  
The Impact

Fc gamma receptor IIB (FcγRIIB) is the only Fc gamma receptor (FcγR) which negatively regulates the immune response, when engaged by antigen- (Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of FcγRIIB on immune protection againstFrancisella tularensis(Ft), a Category A biothreat agent. We utilized inactivatedFt(iFt) as an immunogen. Naïve and iFt-immunized FcγRIIB knockout (KO) or wildtype (WT) mice were challenged withFt-live vaccine strain (LVS). While no significant difference in survival between naïve FcγRIIB KO versus WT mice was observed, iFt-immunized FcγRIIB KO mice were significantly better protected than iFt-immunized WT mice.Ft-specific IgA in serum and bronchial alveolar lavage, as well as IFN-γ, IL-10, and TNF-αproduction by splenocytes harvested from iFt-immunized FcγRIIB KO, were also significantly elevated. In addition, iFt-immunized FcγRIIB KO mice exhibited a reduction in proinflammatory cytokine levelsin vivoat 5 days after challenge, which correlates with increased survival followingFt-LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of FcγRIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.

Phase I trial of recombinant interferon gamma in cancer patients.

1986 ◽  
Vol 4 (2) ◽  
pp. 137-146 ◽  
Author(s):  
S Vadhan-Raj ◽  
A Al-Katib ◽  
R Bhalla ◽  
L Pelus ◽  
C F Nathan ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Phase 1 ◽  
Rest Period ◽  
Lymphocytic Leukemia ◽  
Fixed Dose ◽  
Rapid Decline ◽  
Recombinant Interferon ◽  
Advanced Malignancy

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks. After a 2-week rest period, the IV treatment cycle was repeated. Responders were maintained on repeated IV treatment cycles or daily intramuscular (IM) injections. Patients were entered at fixed dose levels of 0.1, 0.5, or 1.0 mg/m2/d. The maximum safely tolerated dose was 0.5 mg/m2. The most common side effects were constitutional symptoms, including fever, chills, fatigue, and myalgias. Reversible and transient increases in hepatic transaminase and decrease in granulocyte counts were seen. Treatment was associated with a dose-dependent increase in serum levels of beta 2 microglobulin. Partial responses (PRs) were observed in one patient with Hodgkin's disease and one patient with chronic lymphocytic leukemia. Fairly constant levels of serum IFN were found at four and six hours during infusion, followed by a rapid decline within one to two hours. We conclude that rIFN-gamma can be safely administered by a six-hour IV infusion and that it can induce in vivo some of the biologic effects reported in in vitro studies.

Placental MHC class I antigen expression is induced in mice following in vivo treatment with recombinant interferon-gamma

1991 ◽  
Vol 19 (2) ◽  
pp. 115-129 ◽  
Author(s):  
R. Mattsson ◽  
R. Holmdahl ◽  
A. Scheynius ◽  
F. Bernadotte ◽  
A. Mattsson ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Interferon Gamma ◽  
Antigen Expression ◽  
Class I ◽  
Recombinant Interferon ◽  
Mhc Class I Antigen ◽  
In Vivo Treatment

Fc-Gamma Receptor IIIa and Interferon-Gamma SNPs Do Not Predict Responsiveness of Follicular Lymphoma to Galiximab (Anti-CD80 Antibody).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3292-3292 ◽  
Author(s):  
Myron Czuczman ◽  
Bryan R. Leigh ◽  
Thomas E. Witzig ◽  
Julie M. Vose ◽  
Anas Younes ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Clinical Response ◽  
Interferon Gamma ◽  
Peripheral Blood ◽  
Costimulatory Molecule ◽  
Tumor Burden ◽  
Nucleotide Polymorphisms ◽  
Fc Gamma Receptor ◽  
High Affinity ◽  
Gamma Receptor

Abstract CD80 is an immune costimulatory molecule expressed on the cell surface of follicular and other lymphomas. Galiximab, a macaque-human chimeric anti-CD80 monoclonal antibody, has been shown to have antitumor activity in patients with relapsed or refractory, follicular lymphoma. Preclinical work suggested antibody-dependent cellular cytotoxicity (ADCC) as a mechanism for galiximab-induced cell lysis. Single-nucleotide polymorphisms (SNPs) for high-affinity Fc gamma receptor IIIa and high interferon-gamma production have been associated with increased ADCC activity. For this report, genomic DNA from peripheral blood of clinical study patients was analyzed for Fc gamma receptor IIIa and interferon-gamma gene SNPs after PCR amplification. In addition, the frequency of interferon-gamma secreting cells in peripheral blood samples was evaluated by ELISPOT. SNP and ELISPOT results were then evaluated for correlation with clinical response (CR or PR) to galiximab and reduction in tumor burden (SPD of indicator lesions). Of 35 follicular lymphoma patients evaluable for response to galiximab, 2 CRs and 1 PR were observed; time to best response was delayed (Months 3, 9, and 12). Of 34 patients with Fc gamma receptor IIIa SNP results, 6 were homozygous for the high-affinity receptor. Of 33 pts with interferon-gamma SNP results, 4 were homozygous for the high-producing allele. None of the 3 responders were homozygous for high-affinity Fc gamma receptor IIIa or high interferon-gamma production, and the degree of tumor burden reduction was smaller in these homozygotes than in the others. In addition, pretreatment interferon-gamma ELISPOT data did not predict clinical response to galiximab or tumor burden reduction. In summary, high-affinity Fc gamma receptor IIIa and high interferon-gamma production do not predict clinical responsiveness of follicular NHL to galiximab, suggesting that ADCC may not be a primary mechanism of action for this antibody. Ongoing studies are evaluating other potential mechanisms including the immunomodulatory effects of blocking CD80.

in vivo effects of combination treatment with recombinant interferon-gamma and -alpha in metastatic melanoma

1989 ◽  
Vol 43 (6) ◽  
pp. 1001-1006 ◽  
Author(s):  
Susanne Osanto ◽  
Rumo Jansen ◽  
Albert M. I. H. Naipal ◽  
Jan-Willem Gratama ◽  
Aad Van Leeuwen ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Interferon Gamma ◽  
Combination Treatment ◽  
Recombinant Interferon ◽  
In Vivo Effects
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