A5101967257- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Biosimilars and Bioanalytical Methods
- Glycosylation and Glycoproteins Research
- Radiopharmaceutical Chemistry and Applications
- Calcium signaling and nucleotide metabolism
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Advanced Biosensing Techniques and Applications
- Cytomegalovirus and herpesvirus research
- Lymphoma Diagnosis and Treatment
- Ion Channels and Receptors
- Synthesis and Biological Evaluation
- Prostate Cancer Treatment and Research
- Acute Lymphoblastic Leukemia research
- Transgenic Plants and Applications
- Cancer Immunotherapy and Biomarkers
- Multiple Myeloma Research and Treatments
- 3D Printing in Biomedical Research
- Adenosine and Purinergic Signaling
Arsenal Biosciences (United States)
2023-2024
Tenneco (United States)
2017-2021
Menlo School
2019
T-cell-recruiting bispecific antibodies (T-BsAbs) have shown potent tumor killing activity in humans, but cytokine release-related toxicities affected their clinical utility. The use of novel anti-CD3 binding domains with more favorable properties could aid the creation T-BsAbs improved therapeutic windows. Using a sequence-based discovery platform, we identified new from humanized rats that bind to multiple epitopes and elicit varying levels T-cell activation. In T-BsAb format, 12 different...
Therapeutic options currently available for metastatic castration-resistant prostate cancer (mCRPC) do not extend median overall survival >6 months. Therefore, the development of novel and effective therapies mCRPC represents an urgent medical need. T cell engagers (TCEs) have emerged as a promising approach treatment due to their targeted mechanism action. However, challenges remain in clinic limited efficacy TCEs observed thus far solid tumors well toxicities associated with cytokine...
Heavy chain-only antibodies (HCAbs) do not associate with light chains and their VH regions are functional as single domains, forming the smallest active antibody fragment. These ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules may also be attached in series construct multispecific without need protein engineering ensure proper heavy chain pairing. Production human HCAbs has been impeded by fact that natural require association...
We created a novel transgenic rat that expresses human antibodies comprising diverse repertoire of heavy chains with single common rearranged kappa light chain (IgKV3-15-JK1). This fixed-light animal, called OmniFlic, presents unique system for therapeutic antibody discovery and model to study diversity in the context constant chain. The purpose this was analyze variable gene usage, clonotype diversity, describe sequence characteristics antigen-specific monoclonal isolated from immunized...
The therapeutic potential of targeting CD19 in B cell malignancies has garnered attention the past decade, resulting introduction novel immunotherapy agents. Encouraging clinical data have been reported for T cell-based agents, such as anti-CD19/CD3 bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR)-T therapies, acute lymphoblastic leukemia non-Hodgkin lymphoma (B-NHL). However, use both CAR-T therapies limited due to unfavorable pharmacokinetics (PK), significant...
Cluster of differentiation 38 (CD38) is an ecto-enzyme expressed primarily on immune cells that metabolizes nicotinamide adenine dinucleotide (NAD+) to adenosine diphosphate ribose or cyclic ADP-ribose and nicotinamide. Other substrates CD38 include phosphate mononucleotide, a critical NAD+ precursor in the salvage pathway. important coenzyme involved several metabolic pathways required cofactor for function sirtuins (SIRTs) poly (adenosine diphosphate-ribose) polymerases. Declines levels...
8034 Background: T-cell redirecting therapies such as CAR-T cells and engaging bispecific antibodies (T-BsAb) targeting B Cell Maturation Antigen (BCMA) have been highly efficacious against relapsed/refractory myeloma (MM) in early phase clinical studies. However, strongly pan-T cell activating T-BsAbs also shown to overstimulate T cells, inducing toxicity possibly decreasing efficacy. We developed TNB-383B, a fully human BCMA-specific T-BsAb incorporating low-activating αCD3 that...
TPS5092 Background: Prostate cancer (CaP) is the most common in US men. Disseminated CaP invariably progresses to metastatic castrate-resistant prostate (mCRPC). Current treatment options for mCRPC usually lead therapeutic resistance, and novel therapies are urgently needed. PSMA a prostate-specific antigen over-expressed on mCRPC. Antibodies against have been used create T-cell engaging bispecific Abs (TCEs) chimeric receptor T cells, but all such approaches date induce frequent/severe...
8017 Background: Although BCMA is a plasma cell specific surface molecule attractive as an antibody target in multiple myeloma, its scarcity on the may limit efficacy of conventional antibody. T-cell engaging bispecific approaches are highly efficacious and particularly well suited for membrane with limited expression, such BCMA. Teneobio has developed multivalent platform based modular human VH domains, which allowed us to build T antibodies low high agonistic activities. Methods: UniRats...
60 Background: T-cell engaging bispecific antibody (T-BsAb) therapies are highly efficacious and well suited for targets with low expression on tumor cells. Recently, T-BsAbs high activation of CD3 have been shown to overstimulate T cells, leading toxicity decreased efficacy. Teneobio has developed a fully human BCMA-specific T-BsAb using low-activating αCD3 that is effective in vitro vivo against MM but stimulates minimal cytokine release. Methods: UniRats were immunized either or BCMA...
209 Background: Bispecific antibodies that recruit cytotoxic T cells to kill tumor are popular due their targeted mechanism of action. Despite attractiveness, there limitations in the clinic undesirable toxicities associated with cytokine release. We describe here a platform for generation large collection human anti-CD3 obtained from custom transgenic rats. Combining these unique arms different targeting enables creation bispecific varying cell killing capability. These were combined...
Abstract Common challenges of CAR-T cell therapies in solid tumors, such as clear renal carcinoma (ccRCC), include insufficient therapeutic potency and lack tumor specificity. We have developed AB-2100, an autologous integrated circuit T (ICT) product, generated via CRISPR-mediated knock-in a single transgene into safe-harbor locus. AB-2100 encodes transcriptionally regulated sequential AND gate that comprises priming receptor (PrimeR) specific for PSMA inducible CAR targeting CA9 antigen,...
Abstract Common challenges of CAR-T cell therapies in solid tumors, such as clear renal carcinoma (ccRCC), include insufficient therapeutic potency and tumor specificity. AB-2100 is an autologous integrated circuit T product generated via CRISPR-mediated knock-in a single transgene into safe-harbor locus. encodes transcriptionally regulated sequential AND gate that comprises priming receptor (PrimeR) specific for PSMA inducible CAR targeting CA9 antigen, which widely expressed on ccRCC...
57 Background: Multivalent antibodies targeting either CD38 alone or in conjunction with PD-L1 may yield therapeutics superior biological activities and provide benefit for treating malignancies expressing low levels of (MCL, NHL, T cell lymphomas Daratumumab refractory MM). Multivalent, multispecific kill cells through a variety mechanisms including stronger more specific engagement CD38. Potent directed immune checkpoint inhibition is realized by adding an anti-PD-L1 binding domain....
324 Background: Castration resistant prostate cancer (CRPC) remains an incurable disease and new therapeutics are urgently needed. Prostate specific membrane antigen (PSMA) is expressed on the surface of cells expression increases with progression. Therapies directed against PSMA such as radiolabeled antibodies T cell redirecting therapies including chimeric receptor (CAR-Ts) T-cell engaging bispecific (T-BsAbs) have shown promising efficacy in clinical trials but also induce significant...
e17583 Background: Castration resistant prostate cancer (CRPC) is an incurable disease and represents a significant unmet need. Prostate specific membrane antigen (PSMA) protein highly expressed on the surface of cells; expression has been shown to increase with progression. Therapies targeting PSMA, such as anti-PSMA radioligand conjugates, have promise in clinical trials, validating this target for CRPC. T-cell recruiting bispecific antibodies (T-BsAbs) demonstrated potent tumor killing...