Background CD47/SIRPα-based therapies have shown significant promise in cancer treatment, but their development is hindered by widespread CD47 expression on normal cells, especially RBCs, leading to high antibody sink effects and hematologic toxicity such as anemia.1 Recent advances in antibody engineering have enabled the development of more therapeutically relevant anti-CD47 therapeutics, employing novel binding modes… Continue reading 1122 The importance of innovative design in enhancing the safety of the next generation anti-CD47 therapeutics
Tag: Enzyme Kinetics and Mechanisms
1112 Sticky T cells: engineered T cells targeting biglycan on tumor endothelial cells enhance infiltration into metastatic tumors
Background Poor infiltration of therapeutic cells to solid tumors is a major hurdle to success of cell-based therapies.1Upon intravenous administration, only a small fraction (<2%) of these cells infiltrate the tumor.2 3 One of the mechanisms driving exclusion of immune cells from solid tumors is the endothelial cell anergy of angiogenic vessels. Angiogenic vessels have… Continue reading 1112 Sticky T cells: engineered T cells targeting biglycan on tumor endothelial cells enhance infiltration into metastatic tumors
1069 ATG-106, a novel ‘2+1 format CDH6-targeted T-cell engager (TCE), shows potent T cell dependent cytotoxicity and in vivo anti-tumor efficacy
Background Human cadherin-6 (CDH6) is a type II cadherin, containing 5 extracellular domains and a large cytoplasmic domain for the interaction with catenin molecules.1 CDH6 protein localizes to the basolateral membrane of epithelial cells and mediates calcium-dependent cell–cell adhesion.2 Increased CDH6 expression has been identified in several cancer types, including serous-type ovarian cancer, renal cell… Continue reading 1069 ATG-106, a novel ‘2+1 format CDH6-targeted T-cell engager (TCE), shows potent T cell dependent cytotoxicity and in vivo anti-tumor efficacy
1107 Luminescent reporter assays for ADCP and ADCC characterization of immunotherapies targeting primary effector cells
Background Immune system primary effector cells, such as macrophage and natural killer cells, are crucial in combating cancer through mechanisms such as antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC). Both ADCP and ADCC are key mechanisms in antibody-based cancer immunotherapies, beginning when antibodies bind to Fc gamma receptors (FcRs) on the immune cells,… Continue reading 1107 Luminescent reporter assays for ADCP and ADCC characterization of immunotherapies targeting primary effector cells
1067 ATG-201, a novel ‘2+1 CD19-targeted T-cell engager (TCE) for the treatment of B cell malignancies and B cell related autoimmune diseases
Background CD19-targeted therapies, such as chimeric antigen receptor (CAR)-T or T-cell engagers (TCE), have been approved for the treatment of B cell malignancies. By depleting autoreactive B cells, CD19-targeted CAR-T have shown early but encouraging efficacy in treating systemic lupus erythematosus (SLE) patients. However, the clinical application of TCE continues to be greatly hindered by… Continue reading 1067 ATG-201, a novel ‘2+1 CD19-targeted T-cell engager (TCE) for the treatment of B cell malignancies and B cell related autoimmune diseases
1062 Mechanistic QSP modeling and translational strategy for determining an FIH dose for ZW171, a bispecific 2+1 T-cell engager molecule targeting mesothelin and CD3
Background ZW171 is a clinical-stage humanized bispecific T-cell engager (TCE) molecule in a 2+1 antibody format that incorporates two single chain variable fragments (scFvs) that bind to the extracellular domain (ECD) of MSLN, and one fragment antigen binding domain (Fab) that binds to CD3. Binding of the molecule to CD3 on T-cells and MSLN on… Continue reading 1062 Mechanistic QSP modeling and translational strategy for determining an FIH dose for ZW171, a bispecific 2+1 T-cell engager molecule targeting mesothelin and CD3
1101 Affinity maturation and characterization of a novel O-glycan epitope targeting anti-human carcinoma monoclonal antibody (mAb) PB-223
Background Tumor-targeting mAbs can be leveraged to stimulate innate anti-cancer immunity. NEO-102 (Ensituximab) is a chimeric human IgG1 mAb targets a glycosylated variant of MUC5AC with specificity to colorectal and pancreatic cancer. In a phase 2 study, patients with advanced, refractory metastatic colorectal cancer treated with NEO-102 showed promising results. Enhancing binding affinity stands as… Continue reading 1101 Affinity maturation and characterization of a novel O-glycan epitope targeting anti-human carcinoma monoclonal antibody (mAb) PB-223
1095 Designing potent anti-cancer T-cell receptors (TCRs) with structure-enhanced protein language models
Background T-cell receptors (TCRs) are a promising therapeutic modality to drug cancer intracellular targets with cell therapies (engineered T-cells) or biologics (TCR-based T-cell engagers). Effective TCR-based therapeutics usually require higher target-specific affinity or avidity than is common in natural T-cell receptors (PMID: 37891435). To develop such therapeutics, T-cell receptors are usually mutated and selected for… Continue reading 1095 Designing potent anti-cancer T-cell receptors (TCRs) with structure-enhanced protein language models
1089 Engineered primary T cells for degrading tumor-associated extracellular matrix
Background The tumor microenvironment (TME), embedded within the dense fibrous extracellular matrix (ECM) common to many solid tumors, significantly contributes to drug resistance and immunosuppression, thereby reducing the effectiveness of antitumor agents. Increasing the therapeutic dosage in the systemic circulation often fails to improve efficacy and typically results in cachexia and morbidity. Therefore, the challenge… Continue reading 1089 Engineered primary T cells for degrading tumor-associated extracellular matrix
1013 Humanized FcRn knockin rat as a powerful model for preclinical pharmacokinetic evaluation
Background The neonatal Fc receptor (FcRn) is the key homeostatic regulator of serum albumin (ALB) and IgG by salvage and recycling them in a pH-dependent way. It has been demonstrated that the pharmacokinetic properties of antibodies can be improved by increasing FcRn affinity.1–3 For instance, N434A mutation IgG1 variants, which had increased binding affinity to… Continue reading 1013 Humanized FcRn knockin rat as a powerful model for preclinical pharmacokinetic evaluation