MediGene AG Publicizes New Bioinformatics Tool To Predict Potential Cross-Reactivity Of Cancer And Virus Antigens
Article in "Bioinformatics" published in collaboration with scientists from Technical University of Munich and Helmholtz Zentrum München
Martinsried/Munich, 16 September 2016. Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T-cell immunotherapies for the treatment of cancer, announced that a scientific article on the assessment of cancer and virus antigens for cross-reactivity in human tissues has been published in the current issue of "Bioinformatics" (Oxford Journals: doi: 10.1093/bioinformatics/btw567). The research results show how closely matching naturally occurring self-antigens for a given sequence of a therapeutic antigen (or epitope) can be predicted by an algorithm using curated datasets. After filtering for predicted immunogenicity, the output results show up as an index and profile of cross-reactivity to the self-antigens in 22 human tissues. This innovative prediction tool allows Medigene to analyze safety and toxicity issues of TCR candidates at an early stage.
Compared to "Expitope", the well-established bioinformatic tool elaborated by the same collaboration between TUM and Medigene, the "iCrossR" algorithm published here works on actual peptide expression levels and advances the analysis to a higher level: Instead of basing the analysis on mRNA expression data, "iCrossR" directly investigates the actual protein data in 22 human tissues. The score resulting from such an analysis describes the potential risk of cross reactivity of TCR candidates against healthy tissues and helps to positively select those that are the most promising. Furthermore, "iCrossR" allows for sorting against potential off-target activity of TCRs caused by mismatches among epitopes.
Prof. Dr. Dolores J. Schendel, CEO and CSO of Medigene AG explains: "Cross-reactivity of epitopes can cause severe side effects in adoptive immunotherapies directed against selected antigens. With the new in silico research tool "iCrossR" described in this publication, we are able to predict cross-reactivity of on-target and off-target toxicities, helping us in the early selection of safer therapeutically relevant target antigens. "
Prof. Dmitrij Frishman, Lab Head of the Department of Bioinformatics at the Technical University Munich (TUM) and working group leader in Institute of Bioinformatics and System Biology (IBIS) at Helmholtz Zentrum München, adds: "In this work, we exclusively focused on assessing the antigens binding to the MHC-I molecules, as this mechanism of immune response involves natural peptides originating inside the cell. Our protocol is aimed to help in development of better immunotherapies, to improve safety, and to avoid or minimize undesirable autoimmune side effects."
The article entitled "Assessment of cancer and virus antigens for cross-reactivity in human tissues" can be found here online: http://www.ncbi.nlm.nih.gov/pubmed/27614350 .
The results have been generated in a research alliance since 2013 between Prof. Dmitrij Frishman and his scientific co-workers, in close cooperation with Prof. Dolores J. Schendel, CEO and CSO of Medigene AG and her research team.
About Medigene's TCR technology:
The TCR technology aims at arming the patient's own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient's tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient's T cells outside the body (ex-vivo). A large number of specific T cells to fight the tumor is thereby made available to patients within a short period of time.
Medigene's technology for T-cell receptor-modified T cells is one of the company's highly innovative and complementary immunotherapy platforms for adoptive T-cell therapy. The TCR therapy is designed to treat patients with high tumor loads. Medigene is preparing the clinical development of its first TCR candidates and is developing a library of recombinant T-cell receptors. Moreover, a Good Manufacturing Practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established. Medigene plans to commence its first own clinical TCR trials in 2017 and a second in 2018.
Medigene AG is a publicly listed (Frankfurt: MDG1, prime standard) biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative complementary treatment platforms to target various types and stages of cancer with candidates in clinical and pre-clinical development. Medigene concentrates on the development of personalized T cell-based immunotherapies. For more information, please visit www.medigene.com
Martinsried/Munich, 16 September 2016. Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T-cell immunotherapies for the treatment of cancer, announced that a scientific article on the assessment of cancer and virus antigens for cross-reactivity in human tissues has been published in the current issue of "Bioinformatics" (Oxford Journals: doi: 10.1093/bioinformatics/btw567). The research results show how closely matching naturally occurring self-antigens for a given sequence of a therapeutic antigen (or epitope) can be predicted by an algorithm using curated datasets. After filtering for predicted immunogenicity, the output results show up as an index and profile of cross-reactivity to the self-antigens in 22 human tissues. This innovative prediction tool allows Medigene to analyze safety and toxicity issues of TCR candidates at an early stage.
Compared to "Expitope", the well-established bioinformatic tool elaborated by the same collaboration between TUM and Medigene, the "iCrossR" algorithm published here works on actual peptide expression levels and advances the analysis to a higher level: Instead of basing the analysis on mRNA expression data, "iCrossR" directly investigates the actual protein data in 22 human tissues. The score resulting from such an analysis describes the potential risk of cross reactivity of TCR candidates against healthy tissues and helps to positively select those that are the most promising. Furthermore, "iCrossR" allows for sorting against potential off-target activity of TCRs caused by mismatches among epitopes.
Prof. Dr. Dolores J. Schendel, CEO and CSO of Medigene AG explains: "Cross-reactivity of epitopes can cause severe side effects in adoptive immunotherapies directed against selected antigens. With the new in silico research tool "iCrossR" described in this publication, we are able to predict cross-reactivity of on-target and off-target toxicities, helping us in the early selection of safer therapeutically relevant target antigens. "
Prof. Dmitrij Frishman, Lab Head of the Department of Bioinformatics at the Technical University Munich (TUM) and working group leader in Institute of Bioinformatics and System Biology (IBIS) at Helmholtz Zentrum München, adds: "In this work, we exclusively focused on assessing the antigens binding to the MHC-I molecules, as this mechanism of immune response involves natural peptides originating inside the cell. Our protocol is aimed to help in development of better immunotherapies, to improve safety, and to avoid or minimize undesirable autoimmune side effects."
The article entitled "Assessment of cancer and virus antigens for cross-reactivity in human tissues" can be found here online: http://www.ncbi.nlm.nih.gov/pubmed/27614350 .
The results have been generated in a research alliance since 2013 between Prof. Dmitrij Frishman and his scientific co-workers, in close cooperation with Prof. Dolores J. Schendel, CEO and CSO of Medigene AG and her research team.
About Medigene's TCR technology:
The TCR technology aims at arming the patient's own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient's tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient's T cells outside the body (ex-vivo). A large number of specific T cells to fight the tumor is thereby made available to patients within a short period of time.
Medigene's technology for T-cell receptor-modified T cells is one of the company's highly innovative and complementary immunotherapy platforms for adoptive T-cell therapy. The TCR therapy is designed to treat patients with high tumor loads. Medigene is preparing the clinical development of its first TCR candidates and is developing a library of recombinant T-cell receptors. Moreover, a Good Manufacturing Practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established. Medigene plans to commence its first own clinical TCR trials in 2017 and a second in 2018.
Medigene AG is a publicly listed (Frankfurt: MDG1, prime standard) biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative complementary treatment platforms to target various types and stages of cancer with candidates in clinical and pre-clinical development. Medigene concentrates on the development of personalized T cell-based immunotherapies. For more information, please visit www.medigene.com