Author
Michael A. Schoenborn
Bio: Michael A. Schoenborn is an academic researcher. The author has contributed to research in topics: Recombinant DNA & Cloning. The author has an hindex of 6, co-authored 8 publications receiving 1889 citations.
Topics: Recombinant DNA, Cloning, Interleukin, Cell culture, Complementary DNA
Papers
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TL;DR: A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated, indicating that IL-15 uses components of the IL-2 receptor.
Abstract: A cytokine was identified that stimulated the proliferation of T lymphocytes, and a complementary DNA clone encoding this new T cell growth factor was isolated. The cytokine, designated interleukin-15 (IL-15), is produced by a wide variety of cells and tissues and shares many biological properties with IL-2. Monoclonal antibodies to the beta chain of the IL-2 receptor inhibited the biological activity of IL-15, and IL-15 competed for binding with IL-2, indicating that IL-15 uses components of the IL-2 receptor.
1,441 citations
TL;DR: Biological characterization indicates that the cloned ligand induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells.
317 citations
TL;DR: Interleukin 1 is a cytokine which mediates a variety of immunoregulatory and inflammatory activities and exhibits a high degree of sequence homology with IL-1 gene products from other mammalian species.
96 citations
TL;DR: Bovine GM-CSF was weakly active in both human and mouse bone marrow proliferation assays and exhibits a high degree of sequence homology with mouse and human GM- CSF at both the nucleotide and amino acid levels.
59 citations
Patent•
09 May 1988
TL;DR: Cloning and expression of DNA segments encoding bovine IL-1alpha, and processes for producing purified BovineIL-1α as a product of recombinant cell culture, are disclosed in this article.
Abstract: Cloning and expression of DNA segments encoding bovine IL-1alpha, and processes for producing purified bovine IL-1alpha as a product of recombinant cell culture, are disclosed.
13 citations
Cited by
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TL;DR: A novel tumor necrosis factor (TNF) family member has been cloned and characterized, and the TRAIL gene is located on chromosome 3 at position 3q26, which is not close to any other known TNF ligand family members.
2,996 citations
TL;DR: Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis.
2,600 citations
TL;DR: RANK and RANKL seem to be important regulators of interactions between T cells and dendritic cells.
Abstract: Dendritic cells are rare haematopoietic cells that reside in a number of organs and tissues. By capturing, processing and presenting antigens to T cells, dendritic cells are essential for immune surveillance and the regulation of specific immunity. Several members of the tumour necrosis factor receptor (TNFR) superfamily are integral to the regulation of the immune response. These structurally related proteins modulate cellular functions ranging from proliferation and differentiation to inflammation and cell survival or deaths. The functional activity of dendritic cells is greatly increased by signalling through the TNFR family member CD40. Here we report the characterization of RANK (for receptor activator of NF-kappaB), a new member of the TNFR family derived from dendritic cells, and the isolation of a RANK ligand (RANKL) by direct expression screening. RANKL augments the ability of dendritic cells to stimulate naive T-cell proliferation in a mixed lymphocyte reaction, and increases the survival of RANK+ T cells generated with interleukin-4 and transforming growth factor (TGF)-beta. Thus RANK and RANKL seem to be important regulators of interactions between T cells and dendritic cells.
2,306 citations
TL;DR: A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.
Abstract: Natural killer (NK) cells are populations of lymphocytes that can be activated to mediate significant levels of cytotoxic activity and produce high levels of certain cytokines and chemokines. NK cells respond to and are important in defense against a number of different infectious agents. The first indications for this function came from the observations that virus-induced interferons alpha/beta (IFN-alpha and -beta) are potent inducers of NK cell-mediated cytotoxicity, and that NK cells are important contributors to innate defense against viral infections. In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production. Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms. However, high levels of IFN-alpha/beta appear to be unique and/or uniquely dominant in the context of viral infections and act to regulate other innate responses, including induction of NK cell proliferation in vivo and overall negative regulation of IL-12 production. A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.
2,198 citations
TL;DR: The current state of understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, is reviewed, and conceptual gaps in knowledge are highlighted.
Abstract: Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules. Insights into the underlying biological mechanisms and functions of these molecules have, however, lagged significantly behind. Such understanding will be essential for the rational design of next-generation immunotherapies. Here, we review the current state of our understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, and highlight conceptual gaps in knowledge. Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1069–86. ©2018 AACR.
1,893 citations