A5065374059- CAR-T cell therapy research
- Cancer Research and Treatments
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
- CRISPR and Genetic Engineering
Neogen (United States)
2024
Ziopharm Oncology (United States)
2018-2021
Boston University
2019
Merrimack Pharmaceuticals (United States)
2016
Human interleukin-12 (hIL-12) is a cytokine with anticancer activity, but its systemic application limited by toxic inflammatory responses. We assessed the safety and biological effects of an hIL-12 gene, transcriptionally regulated oral activator. A multicenter phase 1 dose-escalation trial (NCT02026271) treated 31 patients undergoing resection recurrent high-grade glioma. Resection cavity walls were injected (day 0) fixed dose vector (Ad-RTS-hIL-12). The activator for hIL-12, veledimex...
Abstract Background Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation immune checkpoint signaling, providing the rationale for a combination trial with inhibition. Methods An open-label, multi-institutional, dose-escalation phase I rGBM subjects (NCT03636477) accrued 21 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg)...
2547 Background: Solid tumors present driver mutations in KRAS, TP53, and EGFR genes on their surface the context of human leukocyte antigen (HLA) molecules to T-cell receptors (TCRs) expressed by T cells. Non-viral genetic engineering patient cells with Sleeping Beauty transposon/transposase system can generate mutation-reactive TCR-T Methods: This is a first-in-human phase 1/2 study autologous cell therapy for patients non-small lung (NSCLC), colorectal, endometrial, pancreatic, ovarian...
2020 Background: Ad-RTS-hIL-12 (Ad) is a novel gene therapy candidate conditionally expressing IL-12 under the control of veledimex (V) acting via proprietary RheoSwitch Therapeutic System (RTS) switch with therapeutic window. Intratumoral Ad + oral V monotherapy (Phase 1 study, NCT02026271 ) resulted in new sustained intra-tumor influx activated cytotoxic T cells, consistent an immune-mediated anti-tumor effect improving median overall survival (mOS) subjects recurrent glioblastoma (rGBM)....
TPS9110 Background: The role of the HER3 receptor and its ligand heregulin (HRG) in progression multiple cancers has been well established. Seribantumab (MM-121) is a fully human, monoclonal IgG2 antibody that binds to HRG domain HER3, blocking activity. In retrospective analyses prior seribantumab Phase 2 studies, high levels mRNA appeared predict poor outcome when patients received standard care (SOC) treatment. Addition SOC improved progression-free survival (PFS) with positive (HRG+)...
3038 Background: Ad-RTS-hIL-12 (Ad) is a novel gene therapy candidate expressing IL-12 under the control of an orally administered activator ligand, veledimex (V), through proprietary RheoSwitch Therapeutic System (RTS) switch. This platform reduces systemic toxicity and stimulates anti-cancer T cell immune response. Methods: Two open label trials evaluated tolerability local inducible expression in heavily pretreated patients with metastatic breast cancer (mBC) or recurrent glioblastoma...
TPS2677 Background: The landscape of cancer treatment is evolving with the emergence innovative immunotherapies. Among these, T cell receptor-engineered (TCR-T) therapy has shown promise for patients solid tumor malignancies. Targeting driver mutations, such as KRAS, may offer novel therapeutic options limited options. Oncogenic mutations in KRAS typically involve single-base at genomic hotspot locations. isoform mutated 84% RAS-driven cancers and nearly 100% pancreatic ductal adenocarcinoma...
2510 Background: Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (“Controlled IL-12”), was shown in phase 1 study (NCT02026271) to elicit new and sustained intra-tumoral infiltration T cells co-expression PD-1. We report updated findings following completion enrollment (with follow-up ongoing) for substudy (NCT03636477) evaluating safety tolerability local, Controlled combination nivolumab...
Ad-RTS-hIL-12 (Ad) is a novel gene therapy expressing IL-12 via the RheoSwitch Therapeutic System® switch under control of an oral activator ligand, veledimex (V). We previously reported on open label Phase I trial describing biological activity recombinant with downstream IFN-γ and activation immune system. provide update intratumoral injections Ad (2x1011virus-particles) + V for patients recurrent GBM (rGBM) in Group 1 (G1) (craniotomy, n=31) initial results 2 (G2) (stereotactic...
3040 Background: Interleukin-12 (IL-12), a master regulator of the immune system, results in anti-tumor responses preclinical models, but safe use requires tightly controlled production. This phase 1 trial (NCT02026271) is first to evaluate safety and tolerability Ad-RTS-hIL-12 (Ad) under transcriptional control with veledimex (V) adults grade III or IV gliomas. Methods: Multicenter, 1, open-label, 3 + dose escalation study Ad (a single intratumoral injection, 2 × 10 11 viral particles, Day...
2564 Background: Interleukin-12 (IL-12) results in anti-tumor responses preclinical models but requires tightly controlled production to achieve safety and elicit immune system activation realize efficacy. A phase 1 “main study” (NCT02026271) enrolled subjects with Grade III or IV gliomas who at the time of resection received intratumoral administration a replication-deficient adenovirus expressing IL-12 under control transcriptional switch (Ad-RTS-hIL-12, Ad) regulated by veledimex (V),...
Abstract DIPG, which is the leading cause of pediatric brain cancer death with no effective treatment, has neither a highly immunosuppressive nor inflammatory tumor microenvironment (TME). Therefore, eliciting pro-inflammatory TME may provide therapeutic benefit. We previously demonstrated in adults recurrent glioblastoma that loco-regional delivery interleukin 12 administered under control proprietary transcriptional switch RheoSwitch Therapeutic Systemâ (RTSâ) delivered via...
TPS2679 Background: In 2022 approximately 1.7 million Americans will die from solid cancers. Recently there have been significant advances in the genetic engineering of T lymphocytes to recognize neoantigens on tumors vivo, resulting remarkable cases tumor regression and remission. Cancer cells frequently harbor KRAS, TP53, EGFR somatic hotspot mutations that can be processed presented by HLA as through their T-cell receptor (TCR). These are not present normal tissues; thus, they attractive...
2053 Background: Interleukin-12 (IL-12), a master regulator of the immune system, results in anti-tumor responses preclinical models, but safe use requires tightly controlled production. It was conditionally produced Ph1 “main” study (NCT02026271) subjects with recurrent glioblastoma (rGBM) using replication-incompetent adenovirus modified to express IL-12 under transcriptional control proprietary RheoSwitch Therapeutic System (Ad-RTS-hIL-12, Ad) regulated by dose veledimex (V). Monotherapy...
Abstract Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a novel gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (V, 20 mg) acting via proprietary RheoSwitch Therapeutic System® (RTS®), was shown in phase 1 Main study (NCT02026271) to elicit sustained intra-tumoral activated cytotoxic T-cell response co-expression PD-1. Additionally, showed improved median overall survival (mOS), compared historical controls, subjects recurrent...
Abstract Ad-RTS-hIL-12 (Ad) is a novel gene therapy, conditionally expressing IL-12 via the RheoSwitch Therapeutic System® (RTS®) switch under control of an oral activator ligand, veledimex (V). We previously reported results from 51 subjects (NCT02026271 and NCT03679754) describing biological activity controlled IL-12, safety survival data. Previously, who received Ad+V (20 mg) managed with low-dose dexamethasone in Main study achieved mOS 17.8 months, which approximately twice anticipated...
Abstract Ad-RTS-hIL-12 (Ad) is a gene therapy candidate for intratumoral (IT) delivery that conditionally expresses IL-12 (IL-12) under the transcriptional control of orally administered veledimex (V) acting via RheoSwitch Therapeutic Systemâ switch. Increased PD-1 expression in samples rGBM following Ad+V (ASCO 2020) supports combination immunotherapy with inhibitor. Phase 1 trials as monotherapy and inhibitor revealed encouraging safety survival data. This phase 2 trial (NCT04006119)...
Abstract A published clinical trial of veledimex (V)-regulatable interleukin-12 (IL-12) gene therapy (“Controlled IL-12”) under the control a transcriptional switch (RheoSwitch Therapeutic Systemâ, RTSâ) as monotherapy in recurrent glioblastoma (rGBM) showed sustained infiltration activated T cells within tumor months after treatment (Sci Transl Med. 2019;11(505)). These demonstrated up-regulation immune checkpoint signaling, providing rationale for combination with PD-1 inhibitor, nivolumab...