In Vivo and in Vitro Induction of Il-6 Byquillaja Saponariamolina Triterpenoid Formulations

Behboudi, Shahriar; Morein, Brør; Villacrés-Eriksson, M.

doi:10.1006/cyto.1997.0219

Cited by 34 publications

(33 citation statements)

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“…Although QH-C iscom-matrix did not stimulate IL-4 and IFN-g, we cannot rule out the possibility that other cytokines, such as IL-13 and IL-15, might contribute to drive antibody responses elicited by QH-C. As shown recently, iscoms induce similar types and magnitudes of both B-and T-cell responses in IL-4 knockout and IFN-g-receptor knockout mice compared with wild-type mice [33], indicating that the immunoenhancing capacity of iscoms can bypass the absence of IL-4 or IFN-g. As shown previously, QH-A and QH-C formulations have synergistic effects at a ratio of 7:0:3, i.e. 70% QH-A, 0% QH-B and 30% QH-C [8,9,34]. Supporting those results, we show here that QH-7.0.3 iscom-matrix stimulates both B-and T-cell responses.…”

Section: Iscom-matrix Containing Qh-a Enhances the Primary Antibody Rsupporting

confidence: 89%

“…Modi®cation of these carbohydrates has been shown to reduce the adjuvant activity and toxicity of Quillaja saponin [3]. The QH-A and QH-C fractions have been de®ned by our laboratory and were shown to have different biological activities, as measured by their ability to induce antibody responses [7], and activate APC to produce proin¯ammatory cytokines [8,9]. The present study provides evidence that QH-A and QH-C have different immunomodulatory properties, encompassing the induction of proin¯ammatory cytokines and activation of acquired immune responses.…”

Section: Iscom-matrix Containing Qh-a Enhances the Primary Antibody Rmentioning

confidence: 99%

“…Free QH-B was found to have comparatively high toxicity coupled with potent adjuvant activity, while free QH-C had considerably lower toxicity than QH-B while retaining potent adjuvant activity, as measured by the secondary total antibody response [7]. However, later studies showed that iscom-matrix with a higher QH-A/QH-C ratio stimulated antigen presenting cells (APC) to produce interleukin (IL)-1 and IL-6 [8,9] more ef®ciently than the QH-C iscom-matrix. In addition, the particulate forms of QH-A (iscom-matrix and iscom) are more potent inducers of proin¯ammatory cytokines than free QH-A [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Quillaja Saponin Formulations that Stimulate Proinflammatory Cytokines Elicit a Potent Acquired Cell‐Mediated Immunity

Behboudi

Morein

1999

Scand J Immunol

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We examined the ability of various Quillaja saponins in iscom‐matrix formulations to induce proinflammatory cytokines, such as interleukin (IL)‐1α and IL‐6, and to stimulate acquired immune responses to influenza virus envelope proteins. The A‐fraction of Quillaja saponins (QH‐A) was shown to stimulate antigen‐presenting cells (APC) to produce proinflammatory cytokines, and elicited a high primary antigen‐specific antibody response and potent cell‐mediated responses, as measured by T‐cell proliferation, production of cytokines and cytotoxic T‐lymphocyte (CTL) activity. The C‐fraction of Quillaja saponins (QH‐C) was shown to have a low capacity to stimulate proinflammatory cytokines and elicited low primary antibody and T‐cell responses. However, the QH‐C iscom‐matrix mediated a potent booster effect, resulting in a high secondary antibody response. The ability of APC to discriminate and to respond to QH‐A formulations more efficiently than to QH‐C with release of proinflammatory cytokines, which precedes a potent acquired immune response, identifies an important mechanism through which some adjuvants may exert their immunoenhancing activities.

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Section: Iscom-matrix Containing Qh-a Enhances the Primary Antibody Rsupporting

confidence: 89%

Section: Iscom-matrix Containing Qh-a Enhances the Primary Antibody Rmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quillaja Saponin Formulations that Stimulate Proinflammatory Cytokines Elicit a Potent Acquired Cell‐Mediated Immunity

Behboudi

Morein

1999

Scand J Immunol

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“…Influenza-ISCOMs prepared with ISCOPREP 703 stimulated peritoneal cells to produce IL-6 and induced levels of soluble IL-1 comparable to those obtained with E. coli lipopolysaccharide, a potent IL-1 inducer [74,75]. Immunization of mice with influenza-ISCOMs resulted in increased serum levels of IL-6 and IL-12 [75,76]. Evidence that antigen in ISCOMs is presented to T cells by APC was reported in a study by Villacres-Eriksson [77].…”

Section: Uptake and Presentation Of Iscomsmentioning

confidence: 87%

“…ISCOMs containing purified Quillaia fractions also induce cytokine secretion in vitro. Influenza-ISCOMs prepared with ISCOPREP 703 stimulated peritoneal cells to produce IL-6 and induced levels of soluble IL-1 comparable to those obtained with E. coli lipopolysaccharide, a potent IL-1 inducer [74,75]. Immunization of mice with influenza-ISCOMs resulted in increased serum levels of IL-6 and IL-12 [75,76].…”

Section: Uptake and Presentation Of Iscomsmentioning

confidence: 87%

ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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Dasatinib in imatinib‐resistant or imatinib‐intolerant chronic myeloid leukemia in blast phase after 2 years of follow‐up in a phase 3 study

Saglio

Hochhaus

Goh

et al. 2010

Cancer

115

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BACKGROUND In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.

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In Vivo and in Vitro Induction of Il-6 Byquillaja Saponariamolina Triterpenoid Formulations

Cited by 34 publications

References 0 publications

Quillaja Saponin Formulations that Stimulate Proinflammatory Cytokines Elicit a Potent Acquired Cell‐Mediated Immunity

Quillaja Saponin Formulations that Stimulate Proinflammatory Cytokines Elicit a Potent Acquired Cell‐Mediated Immunity

ISCOMs: an adjuvant with multiple functions

Dasatinib in imatinib‐resistant or imatinib‐intolerant chronic myeloid leukemia in blast phase after 2 years of follow‐up in a phase 3 study

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