Background T cell engagers (TCEs) are a promising class of targeted therapies and recent clinical successes have shown the strong potential of TCEs to drive robust response rates and increase T cell infiltration in solid tumours.1 Intracellular targets presented by HLA provide an opportunity to build next generation TCEs. Among these intracellular targets, PRAME is… Continue reading 1294 Engineering a T cell receptor (TCR) into an antibody drug format provides a novel approach to half-life extended T cell engagers targeting PRAME A2 and PRAME A24
Tag: Enzyme Kinetics and Mechanisms
1297 NEU-002 leverages a cancer specific innate immune pathway to induce immunogenic cell death and stimulate anti-tumor immunity
Background Immunogenic cell death (ICD) inducers are an emerging therapeutic modality that kill cancer cells to activate anti-tumor immunity through antigen liberation and presentation. While this dual mechanism of action has strong potential, cytotoxicity to immune cells, as observed with ICD-inducing chemotherapies, has hampered current therapeutic approaches. We previously showed that N17350, a neutrophil elastase-inspired… Continue reading 1297 NEU-002 leverages a cancer specific innate immune pathway to induce immunogenic cell death and stimulate anti-tumor immunity
1291 Profiling bispecific T-cell engagers: strategies for enhancing potency while minimizing cytokine release
Background CD3 T-cell engagers (TCEs) represent a promising approach in cancer immunotherapy, yet challenges in efficacy and safety have hindered clinical development. To address these barriers, we developed a TCE platform comprised of novel CD3-binding antibodies, bispecific engineering technology, and a high-throughput process for identifying pairs of CD3- and tumor-binding antibodies with desired properties. By… Continue reading 1291 Profiling bispecific T-cell engagers: strategies for enhancing potency while minimizing cytokine release
1336 Bulk and single-cell analysis of tumor microenvironment (TME) reprogramming induced via ACTM-838, a systemically administered microbial-based clinical-stage immunotherapy
Background STACTTM is a modular, genetically engineered live attenuated bacterial platform based on S. Typhimurium (VNP20009). The platform enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration. STACTTM has been engineered to minimize systemic toxicity and is designed to specifically enrich in the TME via auxotrophic dependency on metabolites of the… Continue reading 1336 Bulk and single-cell analysis of tumor microenvironment (TME) reprogramming induced via ACTM-838, a systemically administered microbial-based clinical-stage immunotherapy
1287 Preclinical characterization of MDX2001, a novel tetraspecific T cell engager (CD3/CD28) targeting TROP2 and c-MET in solid tumor malignancies
Background T cell engagers have demonstrated success in treating hematologic malignancies, but they still face limitations for the treatment of solid tumors. ModeX has developed a novel platform termed Lymphocyte Activator and Survival Enhancement Receptor (LASER) antibodies. MDX2001 is a first-in-class tetraspecific LASER recognizing CD3 and CD28 on human T cells and c-MET and TROP2… Continue reading 1287 Preclinical characterization of MDX2001, a novel tetraspecific T cell engager (CD3/CD28) targeting TROP2 and c-MET in solid tumor malignancies
1339 EVOLVE104, a first-in-class ULBP2/5/6-targeting T-cell engager with integrated CD2 co-stimulation, demonstrates a favorable preclinical safety and toxicity profile in cynomolgus monkeys
Background EVOLVE104 is the first CD3 T-cell engager (TcE) being developed for solid tumors which utilizes integrated CD2 T-cell co-stimulation to enhance durable T-cell effector function. EVOLVE104 is a tri-specific molecule which targets ULBP2/5/6 on tumor cells and utilizes an affinity-tuned CD3 binder together with a CD2-selected fusion protein to deliver coordinated co-stimulatory signal integration… Continue reading 1339 EVOLVE104, a first-in-class ULBP2/5/6-targeting T-cell engager with integrated CD2 co-stimulation, demonstrates a favorable preclinical safety and toxicity profile in cynomolgus monkeys
1343 A CB21-targeted T cell engager is a promising therapeutic for the treatment of colorectal cancer
Background Colorectal cancer (CRC) remains of high unmet medical need. T cell engagers as a modality have gained attraction in solid tumors, but despite the early data that T cells can infiltrate cold CRC tumors with therapies such as Cibisatamab, treatment remains challenging due to poor target specificity and related on-target off-tumor toxicity. Through our… Continue reading 1343 A CB21-targeted T cell engager is a promising therapeutic for the treatment of colorectal cancer
1344 AR092, a proprietary HLA-G/CD3 T cell engager, induces anti-tumor activity and minimal toxicity in solid tumors
Background HLA-G is highly expressed in various types of cancers. It binds to the inhibitory receptor LILRB1 (leukocyte Ig-like receptor B1) or LILRB2 (leukocyte Ig-like receptor B2) on the cell surface of immune cells including NK, T, and dendritic cells, and inhibits their anticancer function. LILRB1, an HLA-G receptor, is expressed in both resting and… Continue reading 1344 AR092, a proprietary HLA-G/CD3 T cell engager, induces anti-tumor activity and minimal toxicity in solid tumors
1313 BRG399, a novel oral microtubule binding agent, induces tumor regression and immune memory in an orthotopic glioblastoma rat model
Background Glioblastoma (GBM) is largely refractory to immune checkpoint blockers due to the heterogenous nature of this tumor type within individuals as well as a highly immunosuppressive tumor microenvironment (TME). Novel therapeutic avenues are challenged by the necessity of a drug to cross the blood-brain barrier. BRG399 is a brain permeant, non-Pgp substrate binding to… Continue reading 1313 BRG399, a novel oral microtubule binding agent, induces tumor regression and immune memory in an orthotopic glioblastoma rat model
1241 Self-supervised representation learning enables genomic pediction at single-organoid resolution
Background Tumor organoids (TO) have emerged as compelling cancer models due in part to their conserved properties of tumor heterogeneity and 3D structure of the tumor-immune microenvironment. A principal challenge in high-throughput screening experiments is tracking and labeling the somatic states of TOs during clonal and subclonal selection and expansion in the presence of immune… Continue reading 1241 Self-supervised representation learning enables genomic pediction at single-organoid resolution