A5076432907- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Microbial Inactivation Methods
- Toxin Mechanisms and Immunotoxins
- RNA Interference and Gene Delivery
- Chemokine receptors and signaling
- Transgenic Plants and Applications
- Advanced Machining and Optimization Techniques
- Virus-based gene therapy research
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Biomarkers in Disease Mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
General Atomics (United States)
2022
Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a likelihood response to PD-1 blockade. We conducted prospective multicenter phase II trial intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined pembrolizumab in patients advanced melanoma cytotoxic (cpCTL).Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while (200 mg, i.v.) 3 weeks. The primary endpoint objective rate (ORR) by RECIST,...
Abstract Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) have entered the landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness critically needed. Patients Methods: Using mouse models we evaluate immune activation tumor intratumoral IL12 plasmid followed by...
Intratumoral delivery of plasmid IL12 via electroporation (IT-tavo-EP) induces localized expression leading to regression treated and distant tumors with durable responses minimal toxicity. A key driver in amplifying this local therapy into a systemic response is the magnitude composition immune infiltrate tumor. While intratumoral typically increases density CD3+ tumor-infiltrating lymphocytes (TIL), composed broad range T-cell subsets, including activated tumor-specific T cells, less...
Clinical studies have demonstrated that local expression of the cytokine IL-12 drives interferon-gamma and recruits T cells to tumor microenvironment, ultimately yielding durable systemic cell responses. Interrogation longitudinal biomarker data from our late-stage melanoma trials identified a significant on-treatment increase intratumoral CXCR3 transcripts was restricted responding patients, underscoring clinical relevance tumor-infiltrating CXCR3+ immune cells. In this study, we sought...
<h3>Background</h3> Electroporated plasmid IL-12 (TAVO or tavokinogene telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize anti-PD-1 antibodies patients predicted as non-responders anti-PD-1.<sup>1 2</sup> Interim data from stage III/IV melanoma actively progressing on antibody are presented herein. <h3>Methods</h3> Patients confirmed disease progression by RECIST v1.1 after at least 12 weeks of...
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<div>AbstractPurpose:<p>Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) have entered the landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness critically needed.</p>Patients Methods:<p>Using mouse models we evaluate immune activation tumor...
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<div>AbstractPurpose:<p>Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) have entered the landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness critically needed.</p>Patients Methods:<p>Using mouse models we evaluate immune activation tumor...
<p>Table S3</p>
<p>Figure S6</p>
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<p>Figure S5</p>