Purbasa Patnaik
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Occupational and environmental lung diseases
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- Nanoparticle-Based Drug Delivery
- Circular RNAs in diseases
- RNA regulation and disease
- Viral gastroenteritis research and epidemiology
- Immune Cell Function and Interaction
- Animal Virus Infections Studies
- Virus-based gene therapy research
Rapt Therapeutics (United States)
2023-2024
Eli Lilly (United States)
2015
Jaypee Institute of Information Technology
2010
Mesothelin (MSLN) is a glycophosphatidylinositol-linked tumor antigen overexpressed in variety of malignancies, including ovarian, pancreatic, lung, and triple-negative breast cancer. Early signs clinical efficacy with MSLN-targeting agents have validated MSLN as promising target for therapeutic intervention, but therapies improved are still needed to address the significant unmet medical need posed by MSLN-expressing cancers.We designed HPN536, 53-kDa, trispecific, T-cell-activating...
Abstract T cells have a unique capability to eliminate cancer and fight malignancies. Cancer adopted multiple immune evasion mechanisms aimed at inhibiting cells. Dramatically improved patient outcomes been achieved with therapies genetically reprogramming cells, blocking T-cell inhibition by or transiently connecting for redirected lysis. This last modality is based on antibody constructs that bind surface antigen an invariant component of the receptor. Although high response rates were...
<p>Legend for Supplementary Data</p>
Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence systematic studies. It is generally believed that both electrostatic interactions sized based mechanical entrapment contribute virus filtration. In order establish whether the effectiveness correlates with a given filter, counter-ion displacement technique was employed determine ionic capacity for several filters. Two filters...
MicroRNAs have been implicated for the regulation of gene expression.These miRNA are a class single stranded non coding RNAs, formed from endogenous transcripts and measure typically about 19-25 nucleotides in length.They important regulators various biological metabolic functions taking place humans.Many miRNAs show tissue specific expression.Human heart is complex organ which during diseased developed conditions shows differential expression miRNA.Here, we overview recent findings on...
Abstract T cell engagers have compelling clinical activity, but their use is limited by the availability of tumor targets with minimal normal tissue expression. Conditionally active designed to be only in and spare tissues could increase number addressable targets. Here, we describe a engager prodrug platform, named ProTriTAC, that preferentially reduce its on-target/off-tumor toxicity improve safety profile targeting solid antigens. ProTriTACs are based on TriTAC platform three binding...
Abstract Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC highly aggressive, limited therapeutic options lead to poor prognosis for patients. HPN328 a trispecific T cell–activating construct (TriTAC) consisting three binding domains: CD3 binder T-cell engagement, an albumin half-life extension, DLL3 engagement. In vitro assays, rodent models, non-human primates were used assess the activity HPN328....
<p>TriTAC mediated cytotoxic activity in vitro and vivo the hCD3ε mouse model.</p>
<p>IHC staining of NCI-H82 xenograft tumors.</p>
<div>Abstract<p>Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC highly aggressive, limited therapeutic options lead to poor prognosis for patients. HPN328 a trispecific T cell–activating construct (TriTAC) consisting three binding domains: CD3 binder T-cell engagement, an albumin half-life extension, DLL3 engagement. <i>In vitro</i> assays, rodent models, non-human primates...
<p>HPN328 binding selectivity to human DLL1 and DLL4.</p>
<p>Stimulation with anti-human CD3 and anti-mouse CD28 beads induces proliferation activation of T cells from hCD3ε mice.</p>
<p>Structure of HPN328.</p>
<p>TDCC co-cultures show no secretion of cytokines in the presence DLL3 negative tumor cell line.</p>
<p>IHC staining of NCI-H82 xenograft tumors.</p>
<p>HPN328 binds to the MC38-hDLL3 cell line.</p>
<p>Repeat doses of HPN328 treatment in female cynomolgus monkeys leads to transient and dose dependent increases cytokines.</p>
<p>TDCC co-cultures show no T cell activation in the presence DLL3 negative tumor line.</p>
<p>HPN328 purity and biophysical stability.</p>
<p>TriTAC mediated cytotoxic activity in vitro and vivo the hCD3ε mouse model.</p>
<p>Structure of HPN328.</p>
<p>Transient changes in counts of white blood cells, lymphocytes, neutrophils, and monocytes associated with single dose intravenous administration HPN328 to cynomolgus monkeys.</p>
<p>HPN328 binds to the MC38-hDLL3 cell line.</p>
<p>HPN328 treatment in cynomolgus monkeys leads to transient reduction circulating T cells.</p>