The Antibody Society

This is a great opportunity for up-and-coming talent!

Society members receive a 20% discount on Schrödinger's Online Course "Introduction to computational antibody engineering"! Computational molecular modeling tools have proven effective in antibody development and are increasing in use across the antibody discovery industry. The antibody engineers of today will frequently encounter molecular modeling throughout their careers making it critical to have foundational understanding of the relevant tools and methods. This course is ideal for those who wish to develop professionally and expand their CV by earning certification and a badge. When registering for the course, you will be able to choose your preferred start and end date. Within those dates, you will have asynchronous access to the course to work on your preferred schedule. The coupon code for your 20% discount is found in the Members Only section of our website (https://lnkd.in/e6wEmZiW). Or contact us by email at [email protected]. https://lnkd.in/dHuVsGTc

Nammi Therapeutics, Inc. has posted details for a first-in-human Phase 1a/1b study of QXL138AM in participants with locally advanced unresectable and/or metastatic solid tumors and multiple myeloma. QXL138AM is a masked immuno-cytokine comprised of an anti-CD138 IgG1 antibody fused to human interferon alpha 2a. The study is enrolling an estimated 100 participants. #immunocytokines #mAbs https://lnkd.in/dgPJjQaF

Thanks for sharing this thought-provoking article, Mads Daugaard!

Thoughts on evolving management for those in a start-up environment or contemplating joining one...

A newly published review examines use of IL-2 for immunotherapy, providing a historical perspective and offering insights into emerging trends. Cutting to the chase (i.e., from the concluding remarks): We reviewed the evolving understanding of IL-2 biology in the context of immunotherapy, in line with current trends, and summarized recent findings on the impact of IL-2-mediated immunotherapy on the differentiation of exhausted CD8 + T cells. Various efforts have been made to engineer IL-2 to avoid severe side effects and off-target effects caused by IL-2wt. Most of these initiatives have focused on reducing binding to IL-2Rα. Recent findings have underscored the significance of engaging CD25 or targeting antigen-specific CD8 T cells for the therapeutic efficacy of IL-2-mediated therapies, thereby opening new potential avenues for combination therapies with current immune checkpoint treatments. PD1-IL2v is a promising approach for stimulating antigen-specific CD8 + T cells while minimizing off-target side effects. However, as seen in previous clinical studies involving engineered IL-2, encouraging results from preclinical studies do not always translate to positive outcomes in clinical trials. Despite this finding, as advancements continue in this field, we anticipate that new agents derived from our evolving understanding will find a significant place in the future landscape of cancer immunotherapy. https://lnkd.in/e2NMju2R

📣 Announcement! We’re happy to announce that members of The Antibody Society will receive a 10% discount on conference registration for the CDD for Biologics Summit, taking place October 22–24, 2024, in Boston, MA. Join us to explore cutting-edge innovations, automate and streamline data collection, integrate experimental insights, and harness deep learning models to advance complex biologics pipelines! * Download the full event guide: https://ter.li/2vgzwb * Register using our 10% membership discount code: https://ter.li/tg59ow You can find the discount code in the members-only section under Member Discount Codes: https://lnkd.in/e6wEmZiW If you’re interested in joining The Antibody Society, check out the membership benefits here: https://lnkd.in/dM3PZCj If your organization wants to support antibody related research and development, explore our corporate sponsorship opportunities: https://lnkd.in/e_rcfAv #TheAntibodySociety #AntibodyResearch #AISummit #ComputationalBiology #MachineLearning

The paper is open access (link below). From the abstract: Approximately 25% of cancers are preceded by chronic inflammation that occurs at the site of tumor development. However, whether this multifactorial oncogenic process, which commonly occurs in the intestines, can be initiated by a specific immune cell population is unclear. Here, we show that an intestinal T cell subset, derived from interleukin-17 (IL-17)-producing helper T (TH17) cells, induces the spontaneous transformation of the intestinal epithelium. This subset produces inflammatory cytokines, and its tumorigenic potential is not dependent on IL-17 production but on the transcription factors KLF6 and T-BET and interferon-γ. The development of this cell type is inhibited by transforming growth factor-β1 (TGFβ1) produced by intestinal epithelial cells. TGFβ signaling acts on the pretumorigenic TH17 cell subset, preventing its progression to the tumorigenic stage by inhibiting KLF6-dependent T-BET expression. This study therefore identifies an intestinal T cell subset initiating cancer. https://lnkd.in/gJFkmtv3

Congratulations, Hitto Kaufmann and co-authors!

In a paper newly published in mAbs, AstraZeneca authors report a novel bispecific modality they call IL-2-armored GPS molecules, which induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted T cell engager. From the abstract: T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release. https://lnkd.in/efd7rn_G