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

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