0000000000803241
AUTHOR
Katrin Goepfert
Oncolytic Virotherapy as Emerging Immunotherapeutic Modality: Potential of Parvovirus H-1
Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evidence indicates that intratumoral (it) or intravenous (iv) injections of replicative oncolytic viruse…
Molecular landscape of esophageal cancer: implications for early detection and personalized therapy
Esophageal cancer (EC) is one of the most lethal cancers and a public health concern worldwide, owing to late diagnosis and lack of efficient treatment. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are main histopathological subtypes of EC that show striking differences in geographical distribution, possibly due to differences in exposure to risk factors and lifestyles. ESCC and EAC are distinct diseases in terms of cell of origin, epidemiology, and molecular architecture of tumor cells. Past efforts aimed at translating potential molecular candidates into clinical practice proved to be challenging, underscoring the need for identifying novel candidates for …
Influence of the oncolytic parvovirus H-1, CTLA-4 antibody tremelimumab and cytostatic drugs on the human immune system in a human in vitro model of colorectal cancer cells
Bernd Heinrich,* Katrin Goepfert,* Maike Delic, Peter R Galle, Markus MoehlerUniversity Medical Center of the Johannes Gutenberg University Mainz, 1st Department of Internal Medicine, Langenbeckstrasse, Mainz, Germany *These authors contributed equally to this workIntroduction: Tumor-directed and immune-system-stimulating therapies are of special interest in cancer treatment. Here, we demonstrate the potential of parvovirus H-1 (H-1PV) to efficiently kill colorectal cancer cells and induce immunogenicity of colorectal tumors by inducing maturation of dendritic cells (DCs) alone and also in combination with cytostatic drugs in vitro. Using our cell culture model, we have additionally investi…
Supp_1 – Supplemental material for Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial
Supplemental material, Supp_1 for Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial by Michael Nagel, Julia Schulz, Annett Maderer, Katrin Goepfert, Nadine Gehrke, Thomas Thomaidis, Peter C Thuss-Patience, Salah E Al-Batran, Susanna Hegewisch-Becker, Peter Grimminger, Peter Robert Galle, Markus Möhler and Jörn Markus Schattenberg in Tumor Biology
Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives
The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenv…
Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies
Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their cli…
Rational Combination of Parvovirus H1 With CTLA-4 and PD-1 Checkpoint Inhibitors Dampens the Tumor Induced Immune Silencing
The recent therapeutic success of immune checkpoint inhibitors in the treatment of advanced melanoma highlights the potential of cancer immunotherapy. Oncolytic virus-based therapies may further improve the outcome of these cancer patients. A human ex vivo melanoma model was used to investigate the oncolytic parvovirus H-1 (H-1PV) in combination with ipilimumab and/or nivolumab. The effect of this combination on activation of human T lymphocytes was demonstrated. Expression of CTLA-4, PD-1, and PD-L1 immune checkpoint proteins was upregulated in H-1PV-infected melanoma cells. Nevertheless, maturation of antigen presenting cells such as dendritic cells was triggered by H-1PV infected melanom…
Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial
Background:Gastric cancer is common malignancy and exhibits a poor prognosis. At the time of diagnosis, the majority of patients present with metastatic disease which precludes curative treatment. Non-invasive biomarkers which discriminate early from advanced stages or predict the response to treatment are urgently required. This study explored the cytokeratin-18 fragment M30 and full-length cytokeratin-18 M65 in predicting treatment response and survival in a randomized, placebo-controlled trial of advanced gastric cancer.Methods:Patients enrolled in the SUN-CASE study received sunitinib or placebo as an adjunct to standard therapy with leucovorin (Ca-folinate), 5-fluorouracil, and irinote…