On September 25, 2023 Glycotope GmbH (Glycotope) and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association reported to have signed an agreement to explore the potential of combining Glycotope’s antibodies against protein/carbohydrate combined glyco-epitopes (GlycoTargets) with chimeric antigen receptor (CAR) technology developed by the Max Delbrück Center (Press release, Glycotope, SEP 25, 2023, View Source [SID1234635384]).
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CARs are engineered synthetic receptors that function to redirect lymphocytes, most commonly T-cells, to recognise and eliminate cells expressing a specific target antigen. These cell-based therapies have demonstrated exciting results in clinical trials and are rapidly becoming powerful alternatives to conventional treatments for hematologic cancers in particular. However, in some indications, including harder to treat cancers with solid tumors, success has been limited. A major problem facing drug developers is the selection of suitable antigens that are only expressed on tumors, and can therefore be targeted safely. In the scope of the newly established collaboration, highly tumor-specific antibodies developed by Glycotope will be combined with the CAR technology of the Max Delbrück Center to analyze their suitability for the treatment of solid tumors.
"CAR-T cells have dramatically improved the treatment of hematologic malignancies. In stark contrast, CAR-T cells lack efficacy against solid tumors, which by far outnumber incidence and mortality rates of leukemia and lymphoma. Epidemiologically, breast, lung, prostate, and colon cancers are the most common "killers" which cannot be successfully targeted using current T cell therapies," said Dr Armin Rehm, who heads the Translational Tumorimmunology Lab at the Max Delbrück Center. "But antibodies can recognize tumor-associated aberrant glycosylation, making it an attractive and tumor-specific target structure.This feature, together with a broad tumor-specific expression, paves the way for the generation of glycan-redirected CAR-T and NK cells. Thus, we are joining forces for a new generation of CAR-T and NK cells," said Dr Höpken, Head of the Lab Environmental Regulation in Autoimmunity and Cancer at the Max Delbrück Center, and Dr Rehm.
"We are pleased to have gained another renowned collaboration partner and look forward to working with the experienced scientists from Uta’s and Armin’s groups to evaluate how our targeting approach can help advance cellular therapies for solid tumors," added Dr Patrik Kehler, CSO at Glycotope.
Glycotope’s antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Targeting these specific antigens enables broad indication range, long-term treatment potential and reduced on-target/off tumor toxicity, key elements of highly potent therapies. Based on this unrivalled tumor-specificity, Glycotope’s antibodies are highly suitable for a multi-function platform approach with independent modes of action to provide a tailored therapy format for as many patients as possible.
The CAR program at the Max Delbrück Center includes several proprietary antibody binders targeting hematologic tumors. This program involves the development of a full preclinical validation, a clinical scale automated manufacturing platform, and the initiation of two phase I/II clinical trials in collaboration with clinical partners. A comprehensive molecular toolbox of modular CAR components enables rapid integration of new antibody binders. Extensive experience in CAR design, retroviral engineering for CAR transfer, regulatory advice by authorities, and established methodologies to generate T cell and NK cell effector populations for in vitro and in vivo testing will facilitate the implementation of innovative antibodies in our next-generation CAR platform, targeting tumor-associated glycan structures.