TCR-T Therapy Armoring & Enhancement

The deployment of advanced technologies can enhance the therapeutic effects of TCR-T cells. Merging the TCR with diverse enhancement tools like our PD1-41BB costimulatory switch protein results in better efficacy and sustained immune responses, thus augmenting TCR-T cell functionality. Co-expression of the CD40L-CD28 costimulatory switch protein with TCRs can enhance T cell tumor penetration and enables to overcome the immunosuppressive tumor microenvironment (TME).

Modification and tailoring within the TCR constant regions can enhance the anti-tumor functional activity of TCR-T cells and improves safety by reducing the potential for off-target effects. In addition, applying a control mechanism like our iM-TCR for better regulation of TCR-T therapies is beneficial to avoid the over-activation of TCR-T cells and, subsequently, T cell exhaustion resulting in reduced efficacy.

TCR-T Therapy armoring & enhancement publications

Dolores J. Schendel. Front. Oncol. 2023, Volume 13 - 2023 | https://doi.org/10.3389/fonc.2023.1216829
Nadja Sailer*, Ina Fetzer*, Melanie Salvermoser*, Monika Braun, Doris Brechtefeld, Christian Krendl, Christiane Geiger, Kathrin Mutze, Elfriede Noessner, Dolores J. Schendel, Maja Bürdek, Susanne Wilde+, and Daniel Sommermeyer+. Cancers 2022, 14, 1998. doi: 10.3390/cancers14081998
Schlenker, R., Olguín-Contreras, L., Leisegang, M., Schnappinger, J., Disovic, A., Rühland, S., Nelson, P., Leonhardt, H., Harz, H., Wilde, S., Schendel, D. Uckert, W., Willimsky, G. and Noessner, E. Cancer Research, 2017.
Pinto, S., Sommermeyer, D., Michel, C., Wilde, S., Schendel, D, Uckert, W., Blankenstein T., Kyewski, B. 2014. Eur J Immunol. 2014 May 20 [Epub ahead of print].

TCR-T Therapy Optimization Abstracts

CIMT

Medigene Presents Preclinical Data on Optimal Affinity TCRs Targeting the Neoantigen Mutant KRAS

Julia Bittmann, Melanie Salvermoser, Dominik Alterauge, Anne-Wiebe Mohr, Doris Brechtefeld, Mario Catarinella, Petra U Prinz, Maja
Buerdek, Kathrin Davari, Dolores J Schendel and Giulia Longinotti

Poster

7th International Neoantigen Summit

KRAS Mutation-Specific TCR-T Cells are Empowered for Improved Multi-Functionality & Durability by Inclusion of a Costimulatory Switch Protein
Giulia Longinotti

Presentation

CHI’s 8th Annual Immuno-Oncology Summit Europe

MDG1015: a 3rd Generation TCR-T Therapy Incorporating the PD1-41BB Costimulatory Switch Protein, Advancing to the Clinic
Kirsty Crame

Presentation

AACR

TCR-gated control of costimulatory switch protein (CSP) activation in rTCR-T cells expressing PD1-41BB
Maja Buerdek, Petra U. Prinz, Kathrin Mutze, Andrea Coluccio Stefanie Tippmer, Miriam Bosch, Giulia Longinotti, Mario Catarinella, Kathrin Davari, Christiane Geiger, Barbara Loesch, Kirsty Crame, Dolores J. Schendel

Poster

ELRIG-Forum

Evolution by Innovation: Connecting the Dots for TCR-T Therapies
Barbara Lösch

Presentation

CAR-TCR Summit Europe

Developing Effective Methods to Monitor, Track & Assess T-Cell Efficacy In Vivo & In Vitro
Dolores J Schendel

Presentation

SITC

A novel library of optimal affinity KRAS mutation-specific T cell receptors associated with multiple HLAs, in combination with a PD1-41BB armoring and enhancement costimulatory switch receptor
Dolores J Schendel, Giulia Longinotti, Mario Catarinella, Melanie Salvermoser, Julia Bittmann, Kirsty Crame, Kathrin Davari and Selwyn Ho

Poster

ESMO

Mitigation of Tumor Microenvironment-Mediated Immunosuppression Using a PD1-41BB Switch Protein with Optimal Affinity TCRs for First-In-Class, 3rd Generation TCR-T Therapies
Kirsty Crame, Giulia Longinotti, Mario Catarinella, Petra U Prinz, Stefanie Tippmer, Kathrin Mutze, Andrea Coluccio, Melanie Salvermoser, Julia Bittmann, Maja Buerdek, Barbara Loesch, Christiane Geiger, Kathrin Davari, and Dolores J Schendel

Poster

CAR-TCR Summit Boston

Improving TCR-T Therapeutic Persistence and Efficacy with Switch Receptors; Dolores Schendel

Presentation

Immuno-Oncology Summit Europe

PD1-41BB Switch Receptor Technology Added to TCR-Ts Further Enhances Antitumor Activity in vitro and in vivo compared to TCR alone Barbara Lösch

Presentation

 

AACR

T cells co-expressing a highly potent NY-ESO-1-specific TCR and a chimeric PD1-41BB co-stimulatory switch receptor show a favorable polyfunctional profile for the treatment of solid tumors Andrea Coluccio, Stefanie Tippmer, Kathrin Mutze, Petra U Prinz, Maja Buerdek, Barbara Loesch, Kathrin Davari, Giulia Longinotti, Dolores J Schendel

Poster

CAR TCR Europe

Transitioning from a multi modular system to a single automated device for TCR T production; Dolores Schendel

Presentation

CHI Immuno-Oncology Summit

TCR-Ts overcoming TME hurdles by switching immunosuppression to T cell activation with integrated Switch Receptor Technology; Dolores Schendel

Presentation

ESMO Immuno-Oncology Congress

The inducible Medigene T cell receptor ( iM TCR) controls cytotoxicity of tumor specific TCR modified T cells with improved avidity through control of TCR surface expression, Andreas Acs, Adriana Turqueti Neves, Justyna Ogonek, Barbara Loesch, Dolores J. Schendel, Slavoljub Milosevic

Poster

ESMO

T cells transgenic for a highly potent PRAME-specific TCR and a chimeric PD1-41BB co-stimulatory receptor represent a promising approach for the treatment of solid tumors; Maja Bürdek, Ina Fetzer, Nadja Sailer, Melanie Salvermoser, Doris Brechtefeld, Kathrin Mutze, Silke Raffegerst, Monika Braun, René Goedkoop, Susanne Wilde, Daniel Sommermeyer

Poster

TCR-based Therapies Summit

T cells equipped with both a highly potent PRAME-specific T cell receptor and a chimeric PD1-41BB co-stimulatory receptor show superior in vitro and in vivo tumor reactivity; Nadja Sailer, Ina Fetzer, Melanie Salvermoser, Doris Brechtefeld, Maja Bürdek, Kathrin Mutze, Monika Braun, Dolores J. Schendel, Susanne Wilde, Daniel Sommermeyer

Poster

Helping TCR-Ts Meet the Challenges of the TME; Dolores J. Schendel

CIMT 2021

Inducible Medigene T cell receptor (iM-TCR): Controlled cytotoxicity of tumor-specific TCR-modified T cells with improved avidity through control of TCR surface expression; Adriana Turqueti Neves, Andreas Acs, Justyna Ogonek, Barbara Loesch,  Dolores J. Schendel, Slavoljub Milosevic

eTalk

T cells expressing a highly potent PRAME-specific T cell receptor equipped with a PD1-41BB switch receptor show a favorable preclinical safety profile, strong anti-tumor reactivity and superior fitness; Nadja Sailer, Ina Fetzer, Melanie Salvermoser, Doris Brechtefeld, Maja Bürdek, Kathrin Mutze, Monika Braun, Susanne Wilde, Daniel Sommermeyer

eTalk

Tumor specific antigens derived from non-mutated non-coding regions of the genome can be targeted by T-cell receptor-transgenic T cells; Anna Schleicher, Alexandra Kuhlenkamp, Qingchuan Zhao, Krystel Vincent, Claude Perreault, Slavoljub Milosevic, Tiziana Franceschetti, and Daniel Sommermeyer

eTalk

AACR 2021

Combining a PRAME-specific TCR showing potent in vitro and in vivo anti-tumor reactivity and a favorable preclinical safety profile with a PD1-41BB switch receptor results in highly efficient T cells; Ina Fetzer, Nadja Sailer, Melanie Salvermoser, Manon Weis, Christian Krendl, Maja Bürdek, Doris Brechtefeld, Isabella Rampp, Julian Rydzek-Wiesner, Monika Braun, Christian Ellinger, Christiane Geiger, Daniel Sommermeyer, Susanne Wilde

Poster [nomenclature adapted]

Targetable immunogenic tumor specific antigens can be identified in non-coding regions of the genome; Franceschetti T, Zhao Q, Vincent K, Perreault C, Milosevic S and Sommermeyer D

Poster

SITC Annual Meeting 2020

Co-stimulation via PD1 41BB chimeric switch receptor enhances function of TCR T cells in an immune suppressive milieu and under chronic antigen stimulation; Melanie Salvermoser, Maria Gerget , Franziska Hasselmann, Elfriede Noessner, Christian Ellinger, Monika Braun, Dolores J. Schendel, Daniel Sommermeyer and Nadja Sailer

Poster

AACR Virtual Annual Meeting II 

The chimeric co-stimulatory receptor PD1-41BB enhances the function of T cell receptor (TCR)-modified T cells targeting solid tumors; Nadja Sailer, Melanie Salvermoser, Maria Gerget, Sarah Thome, Angelika J. Fischbeck, Svenja Ruehland, Luis F. Olguín-Contreras, Maja Buerdek, Christian Ellinger, Elfriede Noessner, Dolores J. Schendel, Patrik Kehler.

Medigene Immunotherapies GmbH, Planegg/Martinsried, Germany, Helmholtz Zentrum München, Munich, Germany, Medigene AG, Planegg/Martinsried, Germany

Abstract

Poster

CAR TCR Summit 2019

iM-TCR Inducible Medigene T Cell Receptor Dr. Slavoljub Milosevic,

Presentation