Medigene expands end-to-end technology platform through worldwide, exclusive license of a CD40L-CD28 Costimulatory Switch Receptor further enhancing potential to treat solid tumors

Medigene expands end-to-end technology platform through worldwide, exclusive license of a CD40L-CD28 Costimulatory Switch Receptor further enhancing potential to treat solid tumors




Medigene expands end-to-end technology platform through worldwide, exclusive license of a CD40L-CD28 Costimulatory Switch Receptor further enhancing potential to treat solid tumors

  • Medigene accelerates the expansion of its end-to-end platform of multiple, combinable, exclusive and proprietary technologies with the potential to create best-in-class T cell receptor engineered T cell (TCR-T) therapies for patients with solid tumors
  • CD40L-CD28 costimulatory switch receptor engages the broader immune system by interacting with and activating non-tumor cell types residing in the immunosuppressive tumor microenvironment (TME)
  • CD40L-CD28 costimulatory switch receptor provides the potential to break down tumor stroma components allowing better infiltration of engineered T cells into the tumor with greater access to tumor cells

Martinsried/Munich, May 2, 2023. Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today reports it has partnered with Helmholtz Munich to acquire the exclusive, worldwide rights to the CD40L-CD28 costimulatory switch receptor adding to the portfolio of technologies within Medigene’s end-to-end platform.

“The CD40L-CD28 costimulatory switch receptor expands our suite of “Product Enhancement” technologies within our platform and joins our existing PD1-41BB costimulatory switch receptor as a technology that has the potential to further enhance the anti-tumor activity of our TCR-T cells and improve their ability to overcome the immunosuppressive solid tumor microenvironment.” said Prof. Dolores Schendel, Chief Scientific Officer.

“We believe that the beneficial effects of the CD40L-CD28 costimulatory switch receptor may be separate or even complementary to those of our existing technologies. We look forward to generating and sharing the data for this in due course.”

end of press release

About Medigene AG

Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive product development and product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit www.medigene.com

About Medigene’s End-To-End Platform

Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The end-to-end platform includes multiple product development optimization technologies (e.g. Allogeneic-HLA (Allo-HLA) TCR Priming) and enhancement technologies, (e.g. PD1-41BB Switch Receptor, Precision Pairing) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies.

About CD40L-CD28 Costimulatory Switch Receptor

The CD40L/CD40 pathway plays a major role in immune regulation and homeostasis. The CD40L (ligand) is a member of the tumor necrosis family and primarily expressed on activated T cells:

  • CD4+ T cells, where its primary function is in the T cell-mediated activation of dendritic cells (DCs) and monocytes.
  • CD8+ T cells thus promoting their expansion and differentiation through DCs.

CD40 is also present on B cells and expressed on dendritic cells (DCs), monocytes and macrophages as well as by non-hematopoietic cells such as epithelial and endothelial cells.

Expression of CD40 has been confirmed in a wide variety of solid tumors like melanoma, prostate, and lung cancers, as well as in carcinomas of the nasopharynx, bladder, cervix, and ovary.

CD28 is expressed on T cells providing costimulatory signals required for T cell activation and survival.
Thus, the CD40L/CD40 pathway plays a crucial role in activation of T cells.

Medigene´s CD40L-CD28 costimulatory switch receptor may contribute to an enhancement of cellular immune responses in several ways.

  • CD40L expressed on activated T cells and CD40 expressed on DC transmits a signal to the antigen presenting cells that results in upregulation of costimulatory molecules and further stimulation of optimal T cell responses.
  • CD40-expressing tumor cells can be subject to apoptosis by direct interaction with CD40L-CD28-engineered T cells independent of MHC/peptide-specific targeting.
  • CD40 is found in the TME of the tumor endothelium, where engagement with CD40L-CD28-engineered T cells enables upregulation of adhesion molecules, thereby improving T cell infiltration into tumors.

Thus, the CD40L-CD28 costimulatory switch receptor acts via DCs and other non-tumor cells and may provide complementary effects to other switch receptors that exert their effects mainly via PD-1 expressing T cells.

About PD1-41BB Costimulatory Switch Receptor

Checkpoint inhibition via PD-1/PD-L1 pathway:  

Cells of solid tumors are sensitive to killing by activated T cells but can escape this killing activity by producing inhibitory molecules known as ‘checkpoint proteins’, such as the Programmed Death Ligand 1 (PD-L1), on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated. The expression of PD-L1 is an adaptive immune resistance mechanism for tumors that can help them survive and grow.

The 4-1BB (CD137) costimulatory signaling pathway:

Effective T cell immune responses to antigens typically require both a primary antigenic stimulation via the T cell receptor (TCR) and costimulatory signals. The intracellular signaling domains of the 4-1BB protein offer a well-characterized pathway to costimulation and enhanced T cell responses.

Medigene’s PD1-41BB switch receptor turns the tumor’s attempted self-defense mechanism against the tumor by substituting the inhibitory signaling domain of PD-1 with the activating signaling domain of 4-1BB. Therefore, instead of inactivating T cells, the switch receptor delivers an activating signal to TCR-T cells. PD1-41BB-modified TCR-T cells proliferate strongly in the presence of PD-L1-positive tumor cells and kill more tumor cells upon repeated exposure. Additionally, switch receptor signals enable TCR-T cells to function better with low levels of glucose or high levels of TGFß, two conditions characteristic of strongly hostile tumor microenvironments.

This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.

Medigene AG

Pamela Keck
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E-mail: investor@medigene.com

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