Thymic Endocrinology and Prospects for Treating Thymic Involution

Hadden, John W.

doi:10.1007/978-1-4613-0349-7_11

Cited by 5 publications

(7 citation statements)

References 156 publications

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“…Good, M.D., Ph.D., in Minneapolis (JH) and Allan Goldstein in Galveston (PN). A focused interest on the thymus led to studies of thymic endocrinology and of immunopharmacologic means to restore T cells and to improve their function in secondary immuno‐deficiency, as occurs in cancer and aging 3–6 …”

Section: Introductionmentioning

confidence: 99%

“…A focused interest on the thymus led to studies of thymic endocrinology and of immunopharmacologic means to restore T cells and to improve their function in secondary immunodeficiency, as occurs in cancer and aging. [3][4][5][6] In vitro studies with thymic epithelial cells and with prothymocytes, thymocytes, and mature T cells led to immune reconstitution studies in neonatal mice, which showed a natural cytokine mixture (originally named natural cytokine mixture (NCM) and since renamed IRX-2) was active in reversing T lymphocytopenia. The data indicated that the same result could not be achieved with recombinant IL-1, IL-2, or their combination.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical studies with IRX‐2 and thymosin α1 in combination therapy

Naylor¹,

Hadden²

2010

Annals of the New York Academy of Sciences

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Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein with pleiotropic immune enhancing activity. IRX-2 is a primary cell-derived biologic containing multiple cytokines that enhance dendritic cell maturation, promote T-cell growth and differentiation, and inhibit tumor-mediated apoptosis of T cells. IRX-2 is being developed as an immunotherapeutic agent as a novel T-cell adjuvant platform for vaccines as well. Based on their biological activities, thymosin alpha1 and IRX-2 were predicted to exhibit synergistic effects when evaluated in animal and human studies. In animal studies, the combination of IRX-2 and Talpha1 (IRX-3) increased T-cell numbers compared to either alone during recovery from hydrocortisone mediated reduction. IRX-3 further enhanced reduction in tumor burden following chemotherapy compared to IRX-2. Based on these studies, IRX-3 is predicted to be especially important in a setting where reversal of immune suppression due to the presence of tumor, irradiation, and/or chemotherapy is likely to be an important factor in cytokine activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preclinical studies with IRX‐2 and thymosin α1 in combination therapy

Naylor¹,

Hadden²

2010

Annals of the New York Academy of Sciences

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“…The thymus gland is well established as the major organ for T lymphocytopoiesis. While it is most active in youth to generate T lymphocytes, its age‐related involution can be reversed and it can replenish the T cell pool 1 . The alternative source for replenishment lies in the periphery and can, through homeostatic expansion, restore both naïve and memory T cells.…”

Section: Introductionmentioning

confidence: 99%

“…While it is most active in youth to generate T lymphocytes, its age-related involution can be reversed and it can replenish the T cell pool. 1 The alternative source for replenishment lies in the periphery and can, through homeostatic expansion, restore both naïve and memory T cells. The mechanisms for T cell replenishment by the thymus have been intensively studied 2,3 ; however, those associated with homeostatic expansion are less well understood.…”

Section: Introductionmentioning

confidence: 99%

“…A focused interest on the thymus led to studies of thymic endocrinology and of immunopharmacologic means to restore T cells and to improve their function in secondary immunodeficiency, as occurs in cancer and aging. 1,2 In vitro studies with thymic epithelial cells and with prothymocytes, thymocytes, and mature T cells (see Refs. 1, 2) led to immune reconstitution studies in neonatal mice, 8 which showed a natural cytokine mixture (originally named NCM and since renamed IRX-2) was active in reversing T lymphocytopenia.…”

Section: Introductionmentioning

confidence: 99%

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IRX‐2 and Thymosin α1 (Zadaxin) Increase T Lymphocytes in T Lymphocytopenic Mice and Humans

Hadden¹,

Verástegui²,

Hadden³

2007

Annals of the New York Academy of Sciences

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Mouse studies showed a synergy of thymosin alpha1 (Talpha1) and a natural cytokine mixture (IRX-2) in increasing T lymphocyte number and responses. Clinical studies with IRX-2 showed increases of T lymphocytes in lymphocytopenic cancer patients but relatively little effect on irradiated, lymphocytopenic patients. The present phase 1 and 2 study shows that Talpha1 enhances the effect of IRX-2 in these lymphocytopenic patients. Patients (seven) were treated with subcutaneously injected IRX-2 (200 units IL-2 equivalence), Talpha1 (1.6 mg/day) (four patients), or the combination of IRX-2 and Talpha1 (seven patients) daily for 10 days. Peripheral blood lymphocytes (T, B, NK) and subsets (CD4, CD8) were measured at the start of treatment and on day 11. IRX-2 and Talpha1 had little or no significant effect. The combination markedly increased various lymphocyte populations (>350 cells/microL). Four patients followed for 6 weeks displayed sustained increases involving both naïve and memory T cells. Responses to persistent infections were observed in three of the four patients and no significant toxicity was observed. Talpha1 and IRX-2 synergize to increase safely T cells in lymphocytopenic patients.

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Expression and modulation of the Lewis x antigen (CD15) on the T cell line Molt‐4

Schulze‐Forster

Maurer

1997

FEBS Letters

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Thymic Endocrinology and Prospects for Treating Thymic Involution

Cited by 5 publications

References 156 publications

Preclinical studies with IRX‐2 and thymosin α1 in combination therapy

Preclinical studies with IRX‐2 and thymosin α1 in combination therapy

IRX‐2 and Thymosin α1 (Zadaxin) Increase T Lymphocytes in T Lymphocytopenic Mice and Humans

Expression and modulation of the Lewis x antigen (CD15) on the T cell line Molt‐4

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