BioNTech SE’s Post

📃Scientific paper: NanoPDLIM2 enhanced efficacy of PD-1 blockade and chemotherapy in mouse lung cancers Abstract: BACKGROUND: Immune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a bona fide tumor suppressor that is repressed in lung cancer to drive cancer and its chemo- and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement. METHODS: Human clinical samples and data were used to investigate PDLIM2 genetic and epigenetic changes in lung cancer. Using an endogenous mouse lung cancer model faithfully recapitulating refractory human lung cancer and a clinically feasible nano-delivery system, we investigated the therapeutic efficacy, action mechanism, and safety of systemically administrated Pdlim2 expression plasmids encapsulated in nanoparticles (nanoPDLIM2) and its combination with PD-1 antibody and chemotherapeutic drugs. RESULTS: PDLIM2 repression in human lung cancer involves both genetic deletion and promoter methylation. NanoPDLIM2 showed low toxicity, high tumor specificity, antitumor activity, and greatly improved the efficacy of anti-PD-1 and chemotherapeutic drugs, with complete tumor remission in 60% of mice and substantial tumor reduction in the remaining mice by the combination of three therapies. Mechanistically, nanoPDLIM2 increased major histocompatibility complex class I (MHC-I) expression, suppressed multi-drug resistance 1 (MDR1) induction, nuclear Rela and stat 3, and survival... Continued on ES/IODE ➡️ https://etcse.fr/nVxF ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

NIH scientists develop AI tool to predict how cancer patients will respond to immunotherapy : In a proof-of-concept study, researchers at the National Institutes of Health (NIH) have developed an artificial intelligence (AI) tool that uses routine clinical data, such as that from a simple blood test, to predict whether someone’s cancer will respond to immune checkpoint inhibitors, a type of immunotherapy drug that helps immune cells kill cancer cells. The machine-learning model may help doctors determine if immunotherapy drugs are effective for treating a patient’s cancer. The study, published June 3, 2024, in Nature Cancer. https://lnkd.in/e5Uc8utd Chang T, Cao Y, Sfreddo HJ, et al. LORIS robustly predicts patient outcomes with immune checkpoint blockade therapy using common clinical, pathologic and genomic features. Nature Cancer. June 3, 2024. DOI: 10.1038/s43018-024-00772-7.  

Enhertu: A New Era of Targeted Cancer Treatment with Room for Growth Traditionally, cancer treatment targeted specific types of tumors based on their location (e.g., breast cancer, lung cancer). However, a new drug called Enhertu is changing the game. It's the first antibody-drug conjugate (ADC) approved by the US FDA to treat cancers based on a shared molecular feature, HER2, rather than their origin. What is Enhertu and how does it work? Imagine a guided missile. Enhertu is like that, but for cancer cells. It has two key components: 1. Targeting antibody: This part recognizes and attaches to the HER2 protein found on the surface of many cancer cells. 2. Cell-killing payload: Once attached, Enhertu releases a potent drug that kills the cancer cell. Why is this a big deal? Enhertu's "pan-tumor" approval signifies a shift towards a more targeted approach to cancer treatment. It's effective against a range of HER2-positive cancers, including breast, lung, and stomach cancers. This personalized approach offers hope for better treatment outcomes for many patients. Are there any limitations? While Enhertu is a breakthrough, there's room for improvement. The "linker" that connects the antibody to the payload can be unstable, potentially causing side effects. Researchers are actively developing more stable linkers to address this. What's the future of ADCs? The success of Enhertu has sparked a surge in interest in ADCs. Pharmaceutical companies are investing heavily in this field. Interestingly, the possibilities go beyond just killing cancer cells. Scientists are exploring attaching other types of payloads to antibodies, such as immune modulators to boost the body's own defenses against cancer. Overall, Enhertu represents a significant step forward in personalized cancer treatment. With ongoing research to improve linker technology and explore new payloads, ADCs hold immense promise for the future of cancer therapy. #medicalaffairs #clinicaldevelopment #medicaljobs #clinicaljobs https://lnkd.in/efrtTQTh

A few days late to the party, but excited to share that our work on a polymeric Stimulator of Interferon Genes (STING) agonist targeted drug delivery platform for cancer immunotherapy has been published in ACS Central Science! STING agonists are a promising class of cancer immuno-therapeutics, but they suffer from poor efficacy and toxicity in clinical trials partly due to drug delivery challenges. As dendritic cells (DCs) are key players in the cancer-immunity cycle, we sought to develop a DC-targeted STING delivery platform as a potent yet tolerable cancer immunotherapy. We formulated a diamidobenzimidazole (diABZI) STING agonist into a prodrug methacrylate monomer with an intracellular cathepsin-cleavable linker. We co-polymerized our STING monomer with a CD206-targeting mannose monomer to yield the STING drugamer 'polySTING' that targets and selectively deliver the diABZI STING agonist to CD206+ cells. We showed that intravenous immunotherapy with polySTING is tolerable and induces tumor CD8+ T-cell infiltration, increases cross-presenting CD8+ DCs in the tumor microenvironment, and matures multiple DC phenotypes in the tumor-draining lymph node. This all results in superior tumor suppression compared to free diABZI STING agonist in two distinct aggressive murine tumor models. Special thanks to my advisors Patrick Stayton and Suzie Pun for guiding us on this work, and my co-authors Kefan Song and Simbarashe Jokonya, PhD for their pivotal work that realized this publication! #cancer #immunotherapy #STING #polymer #drugdelivery

The aggressive type of cancer accounts for 13% of all lung cancer cases worldwide MAIA Biotechnology has announced that positive results from its preclinical studies for THIO, a treatment for small cell lung cancer (SCLC), have been published in Nature Communications. The findings reported from the research were conducted in collaboration with the University of Texas Southwestern. In the UK, more than 43,000 people are diagnosed with lung cancer every year. In total, SCLC accounts for 13% of all cases of lung cancer worldwide. Despite being less common than non-SCLC (NSCLC), it is more aggressive and rapidly spreads throughout the body. Developed as a second or late line of treatment, THIO is an investigational telomere-targeting agent that is currently in clinical development to evaluate its activity in NSCLC. It works to induce telomerase-dependent telomeric DNA modification, DNA damage responses and selective cancer cell death. Telomeres, as well as the enzyme telomerase, play a role in the survival of cancer cells and their resistance to therapies. Specifically, lung cancer small cells rely on telomerase activity for the proliferation of SCLC. The treatment was reported to have shown a profound and persistent tumour regression in advanced, in vivo cancer models, followed by PD-(L)1 inhibitors by inducing cancer-type-specific immune memory in human and mouse SCLC models. The telomere-targeting agent effectively decreased cancer-initiating cells and diminished tumour-initiation potential in vitro and in vivo. In addition, THIO was highly effective in combination with ionising radiation treatment regiments. “The positive outcomes reported in our publication show THIO’s potential as a new therapeutic approach,” said Vlad Vitoc, chairman and chief executive officer, MAIA. Read more: https://lnkd.in/eFuSzmfY Stay in touch with all the leading stories, events and opportunities by subscribing to our LinkedIn Newsletter here: https://bit.ly/3RbdKtc

Cancer immunotherapy is a type of treatment that mobilizes a patient’s immune system to kill tumor cells. It has been successful in treating certain tumors, but patients frequently have chronic inflammation and immunosuppression, which can limit treatment response. Two independent clinical trials published in Science looked at whether dialing down inflammation using drugs called JAK inhibitors could improve the efficacy of anti–PD-1 immunotherapy in cancer patients. The first Science paper is mainly from the authors at the Scripps Research Institute, and they performed a phase 1/2 trial in patients with relapsed/refractory Hodgkin’s lymphoma. A combination of ruxolitinib and nivolumab resulted in improved clinical efficacy in patients who had previously failed checkpoint blockade immunotherapy. Chinese Antibody Society is an independent non-profit, non-government global professional organization with focus upon antibody-based therapeutics. Our society’s official journal, Antibody Therapeutics (2023 CiteScore: 8.7), is an international peer-reviewed, open access journal published by Oxford University Press. You are welcome to visit the official website of the journal (see link below) and submit your therapeutic antibody related manuscripts to our journal. https://lnkd.in/gsTu_U2 #antibodies #antibody #antibodytherapeutics #mabs #mab #biologics

AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This indication is approved under an accelerated approval based on overall response rate (ORR) and duration of response. Iovance is also conducting TILVANCE-301, a Phase 3 trial to confirm clinical benefit. AMTAGVI is the first and the only one-time, individualized T cell therapy to receive FDA approval for a solid tumor cancer. The proposed mechanism for AMTAGVI offers a new cell therapy approach that deploys patient-specific T cells called TIL cells. When cancer is detected, the immune system creates TIL cells to locate, attack, and destroy cancer. TIL cells recognize distinctive tumor markers on the cell surface of each person’s cancer. When cancer develops and prevails, the body’s natural TIL cells can no longer perform their intended function to fight cancer.

CG Oncology raised an impressive $380million IPO last week (23m common stock shares) for their Phase III bladder cancer trials. Impressive given the climate currently. What is driving this? 👉Interim Analysis: Their lead asset Cretostimogene Grenadenorepvec (CG). According to Data presented at the 24th Annual Meeting of the Society of Urological Oncology (SUO) it showed that 50 of the 60 evaluable patients (75.5%) met the study’s primary endpoint of complete response. 👉Exciting Oncolytics: CG’s dual mechanism of action involves killing tumor cells with an Adenovirus, which then releases pro-inflammatory cytokines to the tumor microenvironment, recruiting cytotoxic T cells, which further kill more tumor cells. 👉Their approach: CG leverages the retinoblastoma (Rb) defective pathways common in urothelial carcinomas. The CG Oncolytic Adenovirus binds to Coxsackievirus and Adenovirus Receptors (CAR). Through further down-signaling (elegantly described on their pipeline) creates the above. 👉High Occurrence: Bladder cancer is the sixth most common cancer type in the U.S.—within bladder cancer, Non-Muscle Invasive Bladder Cancer, which accounts for more than 75% of newly diagnosed bladder cancers in the world. 👉..and recurrence: even after treatment, 50% of patients will have the cancer come back. A deeper and wider elimination of cancer cells through Oncolytics and Immunotherapy will reduce this. 👉High unmet need: This has been approved as both as a FDA Fast Track and Breakthrough Therapy Designation, effective treatments in High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer are still limited. This is demonstrated by the growing need (predicted growth rate of 9.2% and is forecasted $7.52 billion by 2029 just in bladder cancer.) In Summary, a high unmet need, promising interim data, selectively targeting oncolytics which can kill and induce anti-tumor environments = Promising future for CG - but - still an "all-or-nothing" trial. Many will be watching and waiting - wishing luck to all those involved!  

TIGIT, an emerging immune checkpoint target for cancer drugs, is the subject of debate in the immunotherapy world. With recent clinical failures but a wealth of promising studies, anti-TIGIT antibodies can’t be counted out yet. A new review published in Biomarker Research looks at the state of TIGIT-based antibody therapies for cancer and includes the application of our recombinant engineered anti-TIGIT antibody in the preclinical study by Freed-Pastor et al. https://ow.ly/QGHg50QGjgz We are continually committed to engineering tools to enable the new frontier of immunotherapy research, especially for emerging cancer therapy targets like TIGIT that need further study. Our immunotherapy research antibodies are built to generate reliable data, even in vivo, to spur the development of new cancer treatments. https://ow.ly/eplE50QGjgA #Immunotherapy #CancerResearch #AntibodyEngineering

Insight review, findings and directions: Cancer therapy with antibodies Current treatments for most of solid cancers: combination therapy with target therapy; radiation, inhibitors, monoclonal antibodies, ADC - neoadjuvant therapy… nano antibodies… The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells.