Background Increasingly complex molecules developed to treat cancer; i.e. immuno-oncology bispecifics, antibody-drug-conjugates, cell therapy, various cell checkpoint inhibitors, demands mouse model systems able to handle complex biological hypotheses. Evolution of the immune-humanized mouse has allowed scientists to directly test human tumors and molecules in these mice without the need for surrogate molecules. First generations of… Continue reading 1442 Comparison of human immune cell repertoire in five CD34 HSC engrafted NSG/SGM3 mouse strains
Tag: Enzyme Kinetics and Mechanisms
1425 BSI-118, a novel anti-B7H7 antibody antagonizing B7H7-KIR3DL3 signaling pathway without affecting B7H7-TMIGD2 stimulatory signaling pathway
Background Being the youngest known molecule of the B7 family, B7H7 is a newly emerging immune checkpoint with unique immunomodulatory characteristics. B7H7 exerts co-stimulatory activity upon interaction with transmembrane and immunoglobulin domain containing 2 (TMIGD2), a member of CD28 family that mainly expressed on resting or naïve T cells. B7H7 exerts coinhibitory activity through binding… Continue reading 1425 BSI-118, a novel anti-B7H7 antibody antagonizing B7H7-KIR3DL3 signaling pathway without affecting B7H7-TMIGD2 stimulatory signaling pathway
1423 BSI-120, a fully human anti-MICA/B antibody with enhanced Fc receptor function, prevents MICA/B shedding and reinforces anti-tumor immunity
Background Major histocompatibility complex class I chain-related protein A (MICA) and B (MICB) are highly polymorphic transmembrane proteins with low levels of expression at steady state, but are up-regulated on a wide variety of human tumors. MICA/B act as activating ligands for natural killer group 2 member D (NKG2D) which mediates tumor surveillance, enabling elimination… Continue reading 1423 BSI-120, a fully human anti-MICA/B antibody with enhanced Fc receptor function, prevents MICA/B shedding and reinforces anti-tumor immunity
1424 BSI-115, a novel anti-V{gamma}9V{delta}2 agonist monoclonal antibody, promotes V{gamma}9V{delta}2 T cell activity against tumor cells
Background V9V2, also known as T cell antigen receptor, is composed of a chain including V9 (TRGV9) and C (TRGC) and a chain including V2 (TRDV2) and C (TRDC). V9V2 is expressed on V9V2 T cells which represent 1–5% population of all circulating T cells (~95% of circulating T cells1), but it can increase to… Continue reading 1424 BSI-115, a novel anti-V{gamma}9V{delta}2 agonist monoclonal antibody, promotes V{gamma}9V{delta}2 T cell activity against tumor cells
1447 Reprogramming tumor-associated macrophages using an engineered nano-immunomodulatory gemcitabine
Background Infiltration of myeloid-derived suppressor cells (MDSCs) establishes an immune-suppressive tumor microenvironment (TME) in Pancreatic Ductal Adenocarcinoma (PDAC), exacerbated by chronic inflammation and recurrent gemcitabine (GEM) mediated chemotherapy. Consequently, developing an immune-modulatory pro-drug form of GEM, targeting tumor cells and modulating the myeloid-derived suppressive TME & TAMs, holds promise for preventing cancer recurrence and increasing… Continue reading 1447 Reprogramming tumor-associated macrophages using an engineered nano-immunomodulatory gemcitabine
9 Decreased expression of MHC delays the onset of xenogeneic graft versus host disease in PBMC humanized NCG mice providing an enhanced model for oncology studies
Background Humanized mice are specialized animal models that are used to assess the efficacy of human immunotherapies on tumors. Humanized mice incorporate components of the human immune system and are created by injecting human CD34+hematopoietic stem cells (HSCs) or human peripheral blood mononuclear cells (PBMCs) into an immunodeficient mouse. PBMC humanized (HuPBMC) mice recapitulate a… Continue reading 9 Decreased expression of MHC delays the onset of xenogeneic graft versus host disease in PBMC humanized NCG mice providing an enhanced model for oncology studies
321 PD-L1 blockade synergizes with c-Jun overexpression to boost CAR-T cell activity and mediate dramatic tumor control in an aggressive autochthonous model of lung adenocarcinoma
Background CAR-T cell therapy has been remarkably successful for blood cancers, but efficacy in solid tumors has been limited.1 2 In a phase-1 trial, CAR-T cells targeting the tumor-associated antigen ROR1 induced complete responses in 2 of 3 patients with chronic lymphocytic leukemia, but rapidly lost function in patients with non-small cell lung cancer (NSCLC),3… Continue reading 321 PD-L1 blockade synergizes with c-Jun overexpression to boost CAR-T cell activity and mediate dramatic tumor control in an aggressive autochthonous model of lung adenocarcinoma
154 Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens across various cancer types
Background High tumor heterogeneity and low mutational burden in cancers pose significant challenges for immunotherapy. To address this, we developed a novel in silico pipeline to characterize cancer-specific splicing events (neojunctions) expressed ubiquitously across ten cancer types. This approach successfully identified tumor-wide, public, alternatively splicing neoantigens (ASNs) that elicit CD8+ T-cell-mediated cytotoxicity across multiple cancers.… Continue reading 154 Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens across various cancer types
1335 Infectious Bursal Disease Virus (IBDV) as a novel virotherapy for remodeling the tumor microenvironment (TME) and stimulating innate and adaptive immune responses in different murine cancer models
Background Within cancer immunotherapy, oncolytic viruses (OVs) are recognized as a promising and robust treatment approach. This study presents the potential of Infectious Bursal Disease Virus (IBDV), an avian-specific pathogen with no known human zoonosis, as a novel therapeutic agent. We assessed IBDV’s efficacy against several cancer types, including glioblastoma (CT-2A, GL261, and patient-derived stem… Continue reading 1335 Infectious Bursal Disease Virus (IBDV) as a novel virotherapy for remodeling the tumor microenvironment (TME) and stimulating innate and adaptive immune responses in different murine cancer models
1315 A novel T cell engager targeting HLA-A*02:01 TP53-R175H for cancer immunotherapy
Background The tumor suppressor protein p53 (TP53) plays a pivotal role in preventing tumor formation by inducing cell cycle arrest and apoptosis in response to DNA damage. However, TP53 mutations are prevalent across various cancer types, and these mutations not only result in loss of tumor suppressive functions but also confer gain-of-function properties that drive… Continue reading 1315 A novel T cell engager targeting HLA-A*02:01 TP53-R175H for cancer immunotherapy