Background CD40 is a molecule required for activation of antigen-presenting cells (APCs). Agonistic antibodies against CD40 showed promising results in clinical trials for various cancers, however their administration is associated with various adverse events including cytokine release syndrome and hepatotoxicity. One of the approaches to decrease toxicity of agonistic anti-CD40 antibodies is to utilize bispecific… Continue reading 1208 Comparison of receptor occupancy and optimal doses of PD1xCD40 and PDL1xCD40 bispecific antibodies using physiologically based pharmacokinetic modeling
Tag: Enzyme Kinetics and Mechanisms
1222 Integrating MHC-I and MHC-II pathways for neoantigen immunogenicity prediction
Background Accurate neoantigen identification is crucial for assessing neoantigen burden and optimizing cancer vaccine formulation. The concurrent activation of CD4+ and CD8+ T cells is essential for inducing a robust immune response. However, current analytic tools predominantly focus on the MHC-I pathway, typically relying on gene expression level and MHC-binding affinity of mutated peptides, while… Continue reading 1222 Integrating MHC-I and MHC-II pathways for neoantigen immunogenicity prediction
1171 Understanding and mitigating the cytokine release syndrome (CRS) mediated by T cell bispecific antibody (TCB) treatment
Background Cytokine Release Syndrome (CRS) is one of the main safety concerns associated with on-target activity of T cell Bispecific antibodies (TCBs). While dexamethasone is widely used for CRS mitigation, its effects on TCB activity is controversial when used at high clinical doses. This highlights the need to explore the synergy of dexamethasone and Tyrosine… Continue reading 1171 Understanding and mitigating the cytokine release syndrome (CRS) mediated by T cell bispecific antibody (TCB) treatment
1063 Advances in mouse models for the evaluation of T-cell engager therapeutics
Background The success of early cancer immunotherapies has led to the development of novel therapeutics including Chimeric Antigen Receptor (CAR) T-cell therapy, T-cell engagers, pegylated cytokines and in vivo cell reprograming approaches. TCEs are typically multi-specific antibodies directed against the T-cell and one or multiple tumor-associated antigen (TAA), whose therapeutic strategy is to 1) engage… Continue reading 1063 Advances in mouse models for the evaluation of T-cell engager therapeutics
1068 ATG-107, a novel 2+1 CD3-based T cell engager (TCE) targeting FLT3, demonstrates potent preclinical efficacy for the treatment of AML
Background Acute myeloid leukemia (AML) is the most common acute leukemia, with treatment outcomes remaining poor. FMS-like tyrosine kinase 3 (FLT3) is highly expressed in over 80% of AML cases, on both AML blasts and leukemic stem cells, while its expression on hematopoietic stem cells was low. CD3 T cell engaging bispecific antibodies (TCE) redirect… Continue reading 1068 ATG-107, a novel 2+1 CD3-based T cell engager (TCE) targeting FLT3, demonstrates potent preclinical efficacy for the treatment of AML
1138 Engineering 3D living systems with in situ high resolution imaging to capture the dynamics of cancer immunotherapy
Background We have engineered1 a 3D system with perfusion compatible with high resolution microscopy. Perfusion-based culture prevents the diffusion limited growth and reduces stress associated with the accumulation of toxic waste enabling high resolution long duration in situ microscopy. This 3D platform uses Liquid-Like Solids (LLS)2 medium that acts as both a 3D support medium… Continue reading 1138 Engineering 3D living systems with in situ high resolution imaging to capture the dynamics of cancer immunotherapy
1050 Comprehensive characterization of antibody drug conjugates for screening and manufacturing
Background The development and manufacturing of Antibody-Drug Conjugates (ADCs) involves the careful selection of antibodies, the strategic choice of cytotoxic payloads, and thorough characterization to ensure therapeutic efficacy and safety. Despite both antibodies and their payloads being mature drug modalities, the conjugation of antibodies to its payload can be complex. Characterizing and evaluating each step… Continue reading 1050 Comprehensive characterization of antibody drug conjugates for screening and manufacturing
1129 A mixed lineage kinase domain-like derived fusion protein resulting in inescapable immunogenic cell death for use in nanoparticle delivered cancer gene therapy
Background Treatment modalities seek to achieve the cancer free state by inducing tumor cell death whether through small molecule inhibitors, cellular, radiation, immuno or chemo, therapies. Tumors evade the induction of cell death through competing survival pathways. Even when executed to completion, the classical programmed cell death of apoptosis induces immune tolerance impairing further immune… Continue reading 1129 A mixed lineage kinase domain-like derived fusion protein resulting in inescapable immunogenic cell death for use in nanoparticle delivered cancer gene therapy
1071 Improving NK cell anti-tumor efficacy by overcoming CD16 shedding with ADAM17 blockade in a novel multifunctional killer engager complex
Background Shedding of CD16, a potent activating receptor on natural killer (NK) cells that mediates antibody dependent cellular cytotoxicity (ADCC), limits the efficacy of NK cell immunotherapies that depend on this mechanism. Blocking A Disintegrin And Metalloprotease 17 (ADAM17), the enzyme that clips CD16 upon NK cell activation, may overcome this limitation. To achieve this,… Continue reading 1071 Improving NK cell anti-tumor efficacy by overcoming CD16 shedding with ADAM17 blockade in a novel multifunctional killer engager complex
1066 T cell engagers targeting HLA-A*11:01 KRAS-G12D and KRAS-G12V mutations for cancer immunotherapy
Background Mutations in the RAS family are highly prevalent in human cancers, including up to 35% of non-small cell lung, 45% of colorectal, and 95% of pancreatic cancers. Kirsten rat sarcoma viral oncogene homologue (KRAS) is the most frequently mutated RAS oncogene and patients with KRAS mutations have poor responses to standard treatment regimens. Leveraging… Continue reading 1066 T cell engagers targeting HLA-A*11:01 KRAS-G12D and KRAS-G12V mutations for cancer immunotherapy