Medigene AG’s Post

Episode 3.9 The slow rise of TCR-T therapy Listen here: https://lnkd.in/eVfycfpB When the first chimeric antigen receptor T-cell (CAR-T) therapy was approved in 2017, there was a general expectation that T-cell receptor T-cell (TCR-T) therapies would follow shortly afterwards and would greatly expand the range of addressable antigens. Despite considerable efforts, CAR-T therapies are still limited to haematological cancers expressing extracellular antigens, such as CD19 or B-cell maturation antigen (BCMA). Autologous TCR-T therapies can be engineered to target intracellular as well as extracellular peptide antigens presented on the cell surface by human leukocyte antigens (HLAs) and can be more readily used in solid tumors as well as in haematological cancers. Progress has been slow, however, given the complexities involved in both product design and process development. A decade ago, the field grappled with the issue of toxic and sometimes fatal cross-reactions between epitopes present in proteins expressed in healthy tissue and those contained in the targeted tumor antigens. More recently, the great challenge has been to ensure that engineered TCR-T cells are healthy enough to expand and persist once transferred back into patients. This year marks an important milestone for the field, as the FDA is due to grant – or deny – approval of Adaptimmune’s T-cell receptor (TCR) T-cell (TCR-T) therapy Afamitresgene autoleucel (afami-cel) for treating melanoma by 4 August 4. In this episode, we trace the development of the TCR-T technology and sketch out its future possibilities with Selwyn Ho, CEO of TCR-T therapy developer Medigene. © S & S #BIOTECH #BIOTECHNEWS #DRUGDISCOVERY #TCRTtherapy #immunotherapy #celltherapy

Solid tumors are challenging to treat with CAR T-cell therapy. The two major challenges are: Antigen heterogeneity - The diverse expression of target antigens on tumor cells, leading to the risk of tumors becoming resistant. Immunosuppressive tumor microenvironment - A hostile setting that exhausts CAR/TCR T-cells and prevents their tumor infiltration, hindering their cancer-fighting abilities. 🔬💡 Our revolutionary iTANK technology is designed to tackle these obstacles head-on! The technology platform arms CAR/TCR T-cells with a neutrophil-activating protein (NAP) from Helicobacter pylori. This not only combats antigen heterogeneity by inducing a broad immune response against a wide range of tumor antigens but also transforms the "cold," suppressive tumor environment into a "hot," active one that supports immune cell activity and tumor infiltration. iTANK CAR/TCR T-cells significantly enhance the efficacy of CAR/TCR T-cell therapies in solid tumors - making them more effective in reducing tumor growth. Discover our technology:

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers 1. NAD+ = rechargeable battery of biological systems. 2. There are three pathways of NAD+ biosynthesis. 1) Kynureine pathway: de novo synthesis of NAD+ from Tryptophan 2) Preiss-Handler pathway: NAPRT has a main role to make NAD+ from nicotinic acid. 3) Salvage pathway: NAMPT is a key enzyme to make NAD+ from nicotinamide. 3. Cancer cells utilize all pathways to meet their energy demand. 4. Therefore, NAMPT has been considered as a promising target for cancer therapy. 5. Fan groups of ShanghaiTech University have developed a next-generation PROTAC to degrade NAMPT. 6. Treatment with the lead PROTAC and nicotinic acid is efficacious against NAPRT-deficient pan-cancers. Because normal cells retain NAPRT activity and can utilize nicotinic acid, the toxicity of NAMPT-targeting PROTACs is mitigated. https://lnkd.in/ghGQGCr3

𝗔𝗱𝗮𝗽𝘁𝗶𝗺𝗺𝘂𝗻𝗲 𝗥𝗲𝗰𝗲𝗶𝘃𝗲𝘀 𝗙𝗗𝗔 𝗔𝗰𝗰𝗲𝗹𝗲𝗿𝗮𝘁𝗲𝗱 𝗔𝗽𝗽𝗿𝗼𝘃𝗮𝗹 𝗼𝗳 𝗧𝗘𝗖𝗘𝗟𝗥𝗔, 𝘁𝗵𝗲 𝗙𝗶𝗿𝘀𝘁 𝗔𝗽𝗽𝗿𝗼𝘃𝗲𝗱 𝗘𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗲𝗱 𝗖𝗲𝗹𝗹 𝗧𝗵𝗲𝗿𝗮𝗽𝘆 𝗳𝗼𝗿 𝗮 𝗦𝗼𝗹𝗶𝗱 𝗧𝘂𝗺𝗼𝗿. The FDA approved a new type of therapy developed by the biotechnology company Adaptimmune for a rare soft tissue cancer called synovial sarcoma. Tecelra is what’s known as a TCR cell therapy. Like CAR-T therapies, these treatments give a patient’s immune cells special receptors with the ability to recognize a protein flag — in Tecelra’s case, MAGE-A4 — that tumors possess. #cancer #sarcoma #CAR #Tcell #immunotherapy #immunity #biotech #pharmaceutical #innovation #medicine #biology #engineering

A common challenge with CAR T-cell therapies is that many patients, including those experiencing full cancer remission, eventually relapse. To eliminate this problem, a new technique creates a CAR-E therapeutic platform, which causes CAR T cells to form a memory of the cancer cell and spring back into action when the cancer reoccurs. Consisting of a weakened form of the immune-signalling molecule interleukin-2 (IL-2) fused to the antigen that the CAR is designed to bind to, the investigators developed a fully novel therapeutic agent. CAR-E therapy in laboratory cultures of myeloma cells and in animal models of the disease resulted in complete clearance of tumour cells. In addition, long-lasting CAR T cells generated by the therapy could be re-stimulated by re-administering CAR-E. This suggests that patients who relapse after CAR T-cell therapy could be effectively treated with additional doses of CAR-E treatment. Furthermore, CAR-E highlights the potential of patients being treated with smaller numbers of CAR T cells than present, without CAR T-cell expansion processes, as a less time-consuming alternative. https://lnkd.in/ewsAUiRW #medicine #research #healthcare #health #drugdevelopment #pharmaceutical #oncology #cancer #cancerresearch #biomarkers #innovation #technology

𝐁𝐢𝐨𝐡𝐲𝐛𝐫𝐢𝐝 𝐦𝐢𝐜𝐫𝐨𝐫𝐨𝐛𝐨𝐭𝐬 𝐥𝐨𝐜𝐚𝐥𝐥𝐲 𝐚𝐧𝐝 𝐚𝐜𝐭𝐢𝐯𝐞𝐥𝐲 𝐝𝐞𝐥𝐢𝐯𝐞𝐫 𝐝𝐫𝐮𝐠-𝐥𝐨𝐚𝐝𝐞𝐝 𝐧𝐚𝐧𝐨𝐩𝐚𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐭𝐨 𝐢𝐧𝐡𝐢𝐛𝐢𝐭 𝐭𝐡𝐞 𝐩𝐫𝐨𝐠𝐫𝐞𝐬𝐬𝐢𝐨𝐧 𝐨𝐟 𝐥𝐮𝐧𝐠 𝐦𝐞𝐭𝐚𝐬𝐭𝐚𝐬𝐢𝐬. Lung metastasis poses a formidable challenge in the realm of cancer treatment, with conventional chemotherapy often falling short due to limited targeting and low accumulation in the lungs. Here, a microrobot approach using motile algae for localized delivery of drug-loaded nanoparticles is shown to address lung metastasis challenges. The biohybrid microrobot [denoted “algae-NP(DOX)-robot”] combines green microalgae with red blood cell membrane–coated nanoparticles containing doxorubicin, a representative chemotherapeutic drug. Microalgae provide autonomous propulsion in the lungs, leveraging controlled drug release and enhanced drug dispersion to exert antimetastatic effects. Upon intratracheal administration, algae-NP(DOX)-robots efficiently transport their drug payload deep into the lungs while maintaining continuous motility. This strategy leads to rapid drug distribution, improved tissue accumulation, and prolonged retention compared to passive drug-loaded nanoparticles and free drug controls. In a melanoma lung metastasis model, algae-NP(DOX)-robots exhibit substantial improvement in therapeutic efficacy, reducing metastatic burden and extending survival compared to control groups. https://lnkd.in/g3GQGMqS

The tumor microenvironment (TME) consists of the tumor-supplying blood vessels, fibroblasts, various immune cell populations, and the extracellular matrix between these diverse cells. These components are also found in the tissue of normal organs, but their proportion, composition, and functionality have been significantly changed to support the malignant tumor cells in the TME. Using drugs to target the various components of the TME can significantly impact the tumor's malignant behavior and, more importantly, its sensitivity toward other treatments. The significance of TME-targeted drugs lies in their ability to alter the intricate interactions within the TME, including the tumor cells themselves. To effectively test new drug candidates, it is crucial to reconstruct the TME, at least in part, and establish a suitable system to evaluate the response of the recreated components to treatment. We developed a comprehensive platform that, in an easy-to-replicate technique, confronts four different human cells (tumor cells, endothelial cells, fibroblasts, and macrophages) to form spheroids with an intricate architecture, recreating major parts of the TME, including complex pseudo-vascular networks. Treatment effects are recorded by light sheet fluorescence microscopy and translated by an advanced image analysis routine in processable multi-parametric datasets. The detailed data output allows for handling a wide range of potential inquiries. The system proved to be robust, with strong interassay reliability, the effect of TME-targeted drugs can be evaluated side-by-side, and the evaluation procedure allows for a ranked assessment of drug candidates with respect to their therapeutic potential. #TumorMicroEnvironment #DrugDevelopment #CancerTherapy #LightSheetFluorescenceMicroscopy Katrin Heinze Wilhelm Sander-Stiftung The Julius Maximilians University of Würzburg   https://lnkd.in/dQU34bCE

💎💎💎Whatsapp!! 💎💎💎CD5 deletion enhances the antitumor activity of adoptive T cell therapies. The currently available #chimeric #antigen #receptor ( #CAR) #T #cell #therapies have had limited efficacy for a wide range of #solid #cancers and #hematological #malignancies, due in part to CAR T cell #dysfunction. The #scavenger #receptor CD5 is associated with the T cell receptor ( #TCR) and inhibits T cell function. Patel et al. show that #genetic_deletion of #CD5 in #CAR and #TCR T cells enhances expansion, persistence, and #cytotoxicity and is #effective in preclinical solid tumor and hematological malignancy models. These results suggest that CD5 may be a critical negative regulator of CAR T cells that can be therapeutically targeted. ➡ 💎 You can find more pieces of work by clicking here. https://lnkd.in/eSG67K5G https://lnkd.in/dB3s88ei #chimeric #antigen #receptor #CAR #T #cell #therapies

Really interesting design of point-mutated CDR binders, which would only can bind under specific acidic TME. (CAB, in an acidic tumor microenvironment) anti-EpCAM x anti-CD3 bispecific antibody. https://lnkd.in/gcHMaZma

𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭𝐬 𝐢𝐧 𝐎𝐧𝐜𝐨𝐥𝐨𝐠𝐲: 𝐑𝐚𝐝𝐢𝐨𝐩𝐡𝐚𝐫𝐦𝐚𝐜𝐞𝐮𝐭𝐢𝐜𝐚𝐥𝐬 💡Radiopharmaceuticals are a blend of pharmaceuticals and radioactive materials that offer targeted therapy with precision, delivering therapeutic doses directly to cancer cells, while sparing healthy tissue. They contain a radioactive isotope, typically combined with a targeting molecule specific to cancer cells. 💡These radiopharmaceuticals are administered to patients, either orally or intravenously, and once inside the body, emit radiation, which can be in the form of gamma rays or beta particles, depending on the specific isotope used. 💡 The emitted radiation interacts with the cancer cells, damaging their DNA and causing cell death through various mechanisms, including apoptosis or direct cellular destruction. 💡 Radiopharmaceuticals may also indirectly affect nearby cancer cells through the bystander effect, where radiation-induced damage to neighboring cells contributes to overall tumor eradication. 💡The targeting molecule attached to the radiopharmaceutical enables it to bind specifically to receptors or antigens overexpressed on the surface of the cells, facilitating precise delivery of radiation to the tumor site. 💡 This approach minimizes systemic toxicity and reduces side effects compared to traditional radiation therapy, which may affect healthy tissues surrounding the tumor.