Papers by Hendrik Knoetgen
OncoImmunology, 2015
Imposing antigenicity on tumor cells is a key step toward successful cancer-immunotherapy. A cyto... more Imposing antigenicity on tumor cells is a key step toward successful cancer-immunotherapy. A cytomegalovirus-derived peptide recombinantly fused to a major histocompatibility class I complex and a monoclonal antibody can be targeted to tumor cells by antibody-mediated delivery and activate a strong and specific CD8(+) T cell response.
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Nature
Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox pr... more Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox proteins play an important part in regulating this development and also proliferation. They specify embryonic structures along the body axis, and are associated with normal and malignant cell growth. The cell-cycle regulator geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. Here, we show that murine geminin associates transiently with members of the Hox-repressing polycomb complex, with the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and loss-of-function experiments in the chick neural tube demonstrate that geminin modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb-like activity for geminin. The interaction between geminin and Hox proteins prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional activation of reporter and endogenous downstream tar...
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Molecular and cellular biology, 2007
The geminin protein functions both as a DNA rereplication inhibitor through association with Cdt1... more The geminin protein functions both as a DNA rereplication inhibitor through association with Cdt1 and as a repressor of Hox gene transcription through the polycomb pathway. Here, we report that the functions of avian geminin are coordinated with and regulated by cell cycle-dependent nuclear-cytoplasmic shuttling. In S phase, geminin enters nuclei and inhibits both loading of the minichromosome maintenance (MCM) complex onto chromatin and Hox gene transcription. At the end of mitosis, geminin is exported from nuclei by the exportin protein Crm1 and is unavailable in the nucleus during the next G(1) phase, thus ensuring proper chromatin loading of the MCM complex and Hox gene transcription. This mechanism for regulating the functions of geminin adds to distinct mechanisms, such as protein degradation and ubiquitination, applied in other vertebrates.
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Cellular and molecular biology (Noisy-le-Grand, France), 1999
The embryonic organizer represents the major regulatory centre for the establishment of the body ... more The embryonic organizer represents the major regulatory centre for the establishment of the body axes during gastrulation. Here, we discuss the endodermal contributions to the organizer of amphibia, birds and mammals. We differentiate between the definitive, prospective liver endoderm, and the primitive, prospective extraembryonic endoderm, the latter addressed as the hypoblast in birds and the visceral endoderm in mammals. We further discuss the role of the prechordal plate, a mesendodermal tissue underlying the prospective forebrain. Our conclusion points out the similarity of the amphibian and the avian organizer, with a concentration of inductive potentials in time and space. On the other hand, we discuss the unique feature of mammals, that have shifted certain aspects of the head organizer into the anterior visceral endoderm.
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Development (Cambridge, England), 1999
Different types of endoderm, including primitive, definitive and mesendoderm, play a role in the ... more Different types of endoderm, including primitive, definitive and mesendoderm, play a role in the induction and patterning of the vertebrate head. We have studied the formation of the anterior neural plate in chick embryos using the homeobox gene GANF as a marker. GANF is first expressed after mesendoderm ingression from Hensen's node. We found that, after transplantation, neither the avian hypoblast nor the anterior definitive endoderm is capable of GANF induction, whereas the mesendoderm (young head process, prechordal plate) exhibits a strong inductive potential. GANF induction cannot be separated from the formation of a proper neural plate, which requires an intact lower layer and the presence of the prechordal mesendoderm. It is inhibited by BMP4 and promoted by the presence of the BMP antagonist Noggin. In order to investigate the inductive potential of the mammalian visceral endoderm, we used rabbit embryos which, in contrast to mouse embryos, allow the morphological recog...
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Nature, 2004
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Developmental Biology, 2000
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Cancer immunology research, Jan 17, 2015
Tumor cells escape immune eradication through multiple mechanisms including loss of antigenicity ... more Tumor cells escape immune eradication through multiple mechanisms including loss of antigenicity and local suppression of effector lymphocytes. In order to counteract these obstacles, we aimed to direct the unique cytomegalovirus-specific immune surveillance against tumor cells. We developed a novel generation of fusion proteins composed of a tumor antigen-specific full immunoglobulin connected to a single major histocompatibility class I complex bearing a covalently linked virus-derived peptide (pMHCI-IgG). Here, we show that tumor antigen expressing cancer cells decorated with pMHCI-IgGs containing a HLA-A*0201 molecule associated with a cytomegalovirus-derived peptide are specifically eliminated through engagement of antigen-specific CD8+ T cells isolated from peripheral blood mononuclear cell preparations of cytomegalovirus-infected humans. These CD8+ T cells act without additional expansion, pre-activation or provision of co-stimulatory signals. Elimination of tumor cells is in...
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Papers by Hendrik Knoetgen