Immunotherapy with natural interleukins and/or thymosin α1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice

Hadden, John W.; Saha, A.; Sosa, Marina; Hadden, Elba M.

doi:10.1016/0192-0561(95)00069-e

Cited by 29 publications

(27 citation statements)

References 23 publications

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“…These cytokines are critical mediators of T cell activation, proliferation, and the formation of a T H 1 response. The activity of IRX-2 on T cells has been investigated previously in mice 36 and confirmed on human T cells (our unpublished data); however, the ability of IRX-2 to also activate and mature DC is a novel finding and is physiologically relevant as the combination of these functions is vital for a coordinated immunologic response. In fact, recent studies have underscored the importance of crosstalk between T cells and DC, including adoptively transferred T cells and DC vaccines.…”

Section: Discussionmentioning

confidence: 89%

IRX-2, a Novel In Vivo Immunotherapeutic, Induces Maturation and Activation of Human Dendritic Cells In Vitro

Egan¹,

Quadrini²,

Santiago‐Schwarz

et al. 2007

Journal of Immunotherapy

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IRX-2 is a uniform, well-defined set of natural cytokines currently in Phase II clinical trials for squamous cell carcinoma of the head and neck (HNSCC). In preliminary clinical studies of HNSCC patients, IRX-2 therapy has shown promising results, increasing overall survival of patients from 32% to 61% at 48 months. Although it is known that specific cytokines in IRX-2 enhance T cell activity [e.g., interleukin-2 (IL-2), interferon-gamma, IL-1beta], we chose to investigate the influence of IRX-2 on monocyte-derived dendritic cells (Mo-DCs) isolated from human peripheral blood in an effort to further understand the clinical findings. We show here that IRX-2 treatment of human monocyte-derived DC resulted in morphologic, phenotypic, and functional changes consistent with the development of mature activated DC. Specifically, IRX-2-treated DC increased expression of CD83 and CCR7, markers for DC maturation and migration, respectively, and increased the expression of HLA-DR, CD54, and the costimulatory molecules CD86 and CD40, which are critical mediators of T cell activation. Functional changes in DC induced by IRX-2 included a reduced endocytic capacity, increased ability to stimulate T cells and increased IL-12 cytokine production. These results provide a plausible mechanistic explanation for the in vivo clinical activity of IRX-2 and an additional rationale for the use of IRX-2-based immunotherapy in patients.

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Section: Discussionmentioning

confidence: 89%

IRX-2, a Novel In Vivo Immunotherapeutic, Induces Maturation and Activation of Human Dendritic Cells In Vitro

Egan¹,

Quadrini²,

Santiago‐Schwarz

et al. 2007

Journal of Immunotherapy

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“…Tα 1 has been shown to promote T-cell dif- Fig. 1 Comparison of accumulated survival rate between treatment group and control group ferentiation and/or maturation [8] , increase production of IFN-γ, IL-2, IL-3 and expression of IL-2 receptor following activation by mitogens or antigens [9,10] , increase NK-cell activity, increase production of migration inhibitory factor, and increase antibody response to T-cell dependent antigens. Moreover, it has been shown to decrease tumor cell growth both in vitro and in vivo and direct antivirus effects [11] .…”

Section: Discussionmentioning

confidence: 99%

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

Cheng

Ding

Shi

et al. 2005

Chinese-German J Clin Oncol

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Objective: To observe the recurrence and prognosis of hepatocellular carcinoma (HCC) patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 (Tα1) postoperatively. Methods: From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups: control group (n=35) received hepatectomy only; treatment group (n=35) received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results: In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% (P =0.0000); HBeAg seroconverted rate was 73.0% vs. 7.5% (P <0.05); the recurrent rate was 10.0 vs 6.5 months (P =0.0032); the median survival time was 12.5 vs. 6.0 months (P =0.0023), respectively. Conclusion: Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.Hepatocellular carcinoma (HCC) is the most common liver tumor in China and ranks second in cancer mortality since the 1990s. Surgical resection is the only potentially curative therapies, however, the long-term prognosis is not yet satisfactory. The main reason is the high recurrence rate after resection of HCC, which has been reported as varying between 20% and 70%, with almost all relapses occurring within 2 years of posthepatectomy [1,2] . Recurrence was not only due to biological characteristic of the tumor and surgical modes, but also closely related to hepatic disease background. In this article we report the preliminary results of the potential efficacy of antivirus therapy using lamivudine and thymosin α 1 (Tα 1 ) in reducing the recurrence and prolonging the survival of HCC patients accompanying with chronic hepatitis B infection with active virus replication after undergoing hepatectomy.

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“…Previous studies indicate that Ta1 may influence T-cell maturation, cytokines production, and functional T-cell subsets [7,13,26,27], and recent work suggests that DC subsets contribute significant polarizing influences on T helper differentiation [15 -17], but the effect Ta1 has on DCs is less clear. In addition, TNFa is one of the molecules capable of inducing DC maturation and IL-12 production in vitro [19 -21].…”

Section: Discussionmentioning

confidence: 99%

“…The drug is also being developed for the treatment of non-small cell lung cancer (NSCLC), hepatocellular carcinoma, AIDS and malignant melanoma [2 -5]. It is evident from previous studies that Ta1 has abilities to affect the maturation, differentiation, and function of T-cells [2,6,7], increase the efficiency of antigen presentation and tumoricidal functions by macrophages [8,9], promote a recovery of normal NK cell activity [10], potentiate the action of cytokines and also reduce the hematological toxicity of cytotoxic drug therapy [4,11], and strengthen the effects of immunomodulators in immunodeficiencies, autoimmune diseases, and neoplastic malignancies [12]. However, little is known about what action Ta1 has on dendritic cells (DCs), which are the most effective antigen presenting cells (APCs) and play an important role in immune response.…”

Section: Introductionmentioning

confidence: 99%

The modulation of thymosin alpha 1 in the maturation, differentiation and function of murine bone marrow-derived dendritic cells in the absence or presence of tumor necrosis factor-alpha

Yin

Chen

Zhou

et al. 2004

International Immunopharmacology

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Immunotherapy with natural interleukins and/or thymosin α1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice

Cited by 29 publications

References 23 publications

IRX-2, a Novel In Vivo Immunotherapeutic, Induces Maturation and Activation of Human Dendritic Cells In Vitro

IRX-2, a Novel In Vivo Immunotherapeutic, Induces Maturation and Activation of Human Dendritic Cells In Vitro

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

The modulation of thymosin alpha 1 in the maturation, differentiation and function of murine bone marrow-derived dendritic cells in the absence or presence of tumor necrosis factor-alpha

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