TY - JOUR A1 - Sonntag, Katja A1 - Hashimoto, Hisayoshi A1 - Eyrich, Matthias A1 - Menzel, Moritz A1 - Schubach, Max A1 - Döcker, Dennis A1 - Battke, Florian A1 - Courage, Carolina A1 - Lambertz, Helmut A1 - Handgretinger, Rupert A1 - Biskup, Saskia A1 - Schilbach, Karin T1 - Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report JF - Journal of Translational Medicine N2 - Background Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Methods Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ+ T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization. Results A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Conclusions Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial. KW - pancreatic carcinoma KW - therapeutic vaccines KW - neoepitope-derived peptides KW - T-cell responses KW - CDR3 sequences Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239276 VL - 16 ER - TY - THES A1 - Menzel, Moritz T1 - Das Betriebsrentenstärkungsgesetz und seine Auswirkungen auf Geringverdiener. Eine modelltheoretische Analyse T1 - The Act of Strengthening Occupational Pensions and its effects on low-income earner N2 - Vor allem unter Geringverdienern ist die betriebliche Altersversorgung nur unterdurchschnittlich verbreitet. Mit dem zum 01.01.2018 in Kraft getretenen Betriebsrentenstärkungsgesetz und insbesondere dem sogenannten BAV-Förderbetrag (§ 100 EStG) versucht der Gesetzgeber daher, diese Altersvorsorgeform attraktiver zu gestalten und so deren Verbreitung unter Geringverdienern auszuweiten. Dass dieses Ziel zumindest aus modelltheoretischer Sicht erreicht werden kann, zeigen die Ergebnisse dieser Studie auf. Anhand eines deterministischen Rechenmodells werden die finanziellen Vor- und Nachteile verschiedener Vorsorgealternativen aufgedeckt und präzise beziffert. Daneben widmet sich die Arbeit auch den steuer-, sozialversicherungs- und arbeitsrechtlichen Regelungen der betrieblichen Altersversorgung vor und nach Inkrafttreten des Betriebsrentenstärkungsgesetzes und diskutiert darüber hinaus alternative Reformmaßnahmen. N2 - With the Act of Strengthening Occupational Pensions (BRSG - Betriebsrentenstärkungsgesetz), which came into force on January 1, 2018, and in particular the new § 100 EStG (so-called BAV-Förderbetrag - occupational pension subsidy), the legislator is attempting to make company pension schemes more attractive and thus expand their distribution. Especially among low-income earners, occupational pension schemes are only under-average. Due to the demographic development and the resulting decline in the level of security of the statutory pension insurance in the future, additional, capital-funded provision and thus occupational pension schemes will become increasingly important. Especially low-income earners are dependent on additional provisions in order to escape the threat of old age poverty. Against this background, this dissertation examines how and to what extent tax and social security law are able to promote low-income earners before and after the BRSG came into force. This is done using model theory as the main research method. The core of the work is a deterministic calculation model. Its results finally show that the legislator has succeeded in making occupational pension schemes more attractive with the BRSG. Low-income earners in particular are given targeted subsidies with the so-called Riester-incentive and the occupational pension subsidy. The aim of promoting this group of people can therefore be achieved with the reforms undertaken – at least from a model theory point of view. The reasons for the lack of sufficient benefit claims from occupational pension schemes among low-income earners have been and are still being intensively discussed in the expert public. So far, however, there has been a lack of an exact model-theoretical consideration to uncover and precisely quantify possible financial advantages and disadvantages of individual pension alternatives in the light of the BRSG reforms. In particular, the occupational pension subsidy introduced by the new § 100 EStG has not yet been examined in terms of model theory. This dissertation closes these gaps. T3 - Studien zu Rechnungslegung, Steuerlehre und Controlling - 4 KW - Betriebsrentenstärkungsgesetz KW - Altersvorsorge KW - Altersversorgung KW - Betriebsrente KW - Riester-Rente KW - BAV-Förderbetrag KW - Betriebsrentenstärkungsgesetz KW - BRSG KW - Steuern KW - Sozialversicherung KW - Geringverdiener KW - Förderung KW - Modelltheorie KW - Zillmerung KW - Doppelverbeitragung KW - Entgeltumwandlung KW - Pflichtzuschuss KW - Zusage Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191753 SN - 978-3-95826-126-6 SN - 978-3-95826-127-3 N1 - Parallel erschienen als Druckausgabe in Würzburg University Press, 978-3-95826-126-6, 27,80 Euro. PB - Würzburg University Press CY - Würzburg ET - 1. Auflage ER - TY - BOOK A1 - Kiesewetter, Dirk A1 - Grom, Michael A1 - Menzel, Moritz A1 - Tschinkl, Dominik T1 - Optimierungsmöglichkeiten bei den bestehenden steuer- und sozialversicherungsrechtlichen Förderregelungen der betrieblichen Altersversorgung N2 - Germany's old-age retirement system is based on three pillars: the statutory pension scheme, company pension schemes (CPS), and private retirement funds. The current government's coalition agreement expressly foresees a strengthening of CPS since its popularity has heavily stagnated in recent years. The intention is to optimize the fiscal and social insurance-related framework for CPS in an attempt to encourage its wider use. The present expert opinion is a contribution towards this effort. There is considerable potential for this especially among small and medium-sized enterprises (SMEs) and earners of low and very low incomes, since these groups are disproportionately under-represented when it comes to CPS takeup. In light of this, this opinion gives priority to these target groups. The study is structured as follows. First, a comprehensive literature review is provided and guided interviews with experts performed in order to identify obstacles to the continued spread of CPS among the target groups under review. Then, interviews are held with employers in the SME category as well as earners of low and very low incomes in order to verify the obstacles identified during the first step and consider any additional insights. On this basis, the authors consider which reforms may prove effective in addressing the identified obstacles. Here, as instructed, any potential reforms should endeavor not to create a financial burden on Germany’s tax and social insurance authorities. We then subject these reform ideas to an empirical review that involves interviews with SME tax advisers and again with earners of low and very low incomes. Having analyzed these interviews and discussing additional practical considerations, we explicitly recommend the implementation of selected reforms. In doing so, the authors propose the following two concrete recommendations. Recommendation 1 suggests introducing a mandatory employer contribution on top of deferred compensation that corresponds to the amount of social insurance contributions that are saved as a result, of which employees would be the obvious beneficiaries. This would result in an increase in employers' financial burden compared to the status quo. To compensate, a "CPS deduction" would be introduced as a tax incentive for small enter-prises that decide to introduce a CPS for their employees. This deduction would function similarly to the investment deduction option afforded under Section 7g of the German Income Tax Act, resulting in a positive liquidity and tax deferment effect for small enterprises. Recommendation 2 aims at incentivizing employees to participate in a CPS. Two alternatives are offered. Either Germany's existing Riester subsidy system could be better integrated into CPS schemes by eliminating the duplication of contributions that exists under the status quo. Alternatively, a "CPS subsidy" could be introduced. This would involve granting a statutory subsidy to employers that contribute a certain minimum amount to the CPS on behalf of their employees. As a consequence, employees would be able to participate in a CPS without having to make a contribution of their own, which would have the desired effect especially for earners of low and very low incomes. In connection with Recommendation 2, the authors mention two additional aspects that ought to be implemented for the benefit of employees. One, a restriction should be placed on the extent to which CPS payments are set off against basic social security payments. Two, the acquisition costs of insurance-based CPS solutions should be spread across the entire term of the agreement, meaning that no commission fees can be retained that relate to contributions that haven't yet been made. Finally, the authors recommend two measures that serve to flexibilize and simplify the legal framework surrounding CPS: an increase in the tax- and social insurance contribution-exempt total outlay in the presence of insurance-based external funding and, related to this, a switch from an annualized to a lifetime- or length-of-service-based approach. N2 - Angesichts der demografischen Entwicklung setzt die Bundesregierung zur Schließung der drohenden Rentenlücke auch auf die betriebliche Altersversorgung (bAV). Dieses Gutachten entwickelt Empfehlungen an den Gesetzgeber zur Optimierung der steuer- und sozialversicherungsrechtlichen Rahmenbedingungen der bAV. Die Zielvorgabe lautet, die Verbreitung der bAV unter Gering- und Niedrigverdienern zu erhöhen und kleinen und mittleren Unternehmen als Arbeitgeber Anreize zu setzen, ihren Arbeitnehmern ein bAV-Angebot zu unterbreiten. Das Gutachten schafft einen umfassenden Überblick über bestehende Hemmnisse für diese beiden Zielgruppen, an der bAV zu partizipieren. Auf dieser Basis werden zehn Reformüberlegungen erarbeitet und auf ihre Wirkungen hin geprüft. Hieraus ergeben sich jeweils eine Handlungsempfehlung für die Arbeitgeber- und die Arbeitnehmerseite. Außerdem werden Ansatzpunkte für eine Vereinfachung der steuer- und sozialversicherungsrechtlichen Regelungen aufgezeigt. Die Analyse der Hemmnisse und die Kernelemente der Empfehlungen wurden durch Interviews mit Experten und mit Angehörigen der Zielgruppen empirisch abgesichert. KW - Betriebliche Altersversorgung KW - Altervorsorge KW - bAV KW - Altersversorgung Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128597 SN - 978-3-95826-030-6 (print) SN - 978-3-95826-031-3 (online) PB - Würzburg University Press CY - Würzburg ER -