FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2118407113> ?p ?o ?g. }

• W2118407113 abstract "Major obstacles for the development of immunotherapeutics are the ability of tumors to escape the immune system coupled with toxicity associated with systemic administration. To overcome these challenges, we have developed an adenoviral vector, Ad-RTS-IL-12 (AD), administered intratumorally (IT) under control of the RheoSwitch Therapeutic System® (RTS) technology platform. Expression of IL-12 mRNA and IL-12 protein is tightly regulated by the oral administration of a small molecule activator ligand, veledimex (AL). We have previously demonstrated a concentration-related increase in IL-12 mRNA concomitant with increase in expression of IL-12 protein in HT1080 cells transduced with AD and incubated with AL. Removal of AL from the media resulted in a return to baseline IL-12 expression within 48 hours. Results from the subcutaneous 4T1 syngeneic BALB/c mouse mammary tumor model demonstrated an AL dose-related increase in tumor IL-12 mRNA and IL-12 protein expression with the maximum IL-12 tumor protein level of 280 ng/mg achieved at 150 mg/m2 AL + 1e10 vp AD. In addition, a return to baseline IL-12 mRNA and IL-12 protein expression was observed on cessation of AL. The effect of AD + AL on tumor growth rate was evaluated in a subcutaneous 4T1 syngeneic BALB/c mouse mammary tumor model. A single intratumoral injection of 1e10 vp AD combined with oral administration of AL (15, 30, 75 or 150 mg/m2) on a Q1Dx5 schedule led to significant AL dose-related tumor growth inhibition with tumor size reduction of 27%, 37%, 57% and 60%, respectively when compared to vehicle on Day 33. Neither AD or AL alone had an effect on tumor growth rate relative to vehicle control. No change in clinical signs or body weight was observed when compared to vehicle alone. Tumor growth inhibition correlated with an increase in tumor IL-12 levels, a decrease in Tregs, and an increase in cytotoxic T cells. Results from a phase 1 study in melanoma have shown dose-related production of IL-12 and clinical activity in injected and non-injected lesions at 100 and 160 mg of AL. Cytotoxic agents at low doses have been shown to prime the immune system and combination with immunotherapy may augment tumor specific T-cell immune responses resulting in enhanced efficacy. In the 4T1 mouse mammary tumor model Ad-RTS-mIL12 (1e10vp) + AL (30 mg/m2) combined with palifosfamide (40 or 120 mg/m2 QD IP for 3 days) significantly inhibited tumor growth (∼71-90% vs. control) concomitant with increased median survival when compared to the single agents alone. Based on these findings in a multicenter, open-label, randomized, phase 2 study evaluating the safety and efficacy of AD + AL alone or in combination with cytotoxic agents in subjects with recurrent/metastatic breast cancer with accessible tumor(s) is ongoing. This study assesses AD + AL administered as a monotherapy and a combination therapy. In the monotherapy arm, AD is administered IT on Day 1 and AL 140 mg is administered orally on either a Q1Dx7 or QODx14 schedule. In the combination arm, palifosfamide 120 mg/m2 IV Q1Dx3 is be administered with AD + AL QODx14 (28 day cycle). Preliminary data show that AD + AL is safe and well tolerated. Preclinical and clinical data will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-02-01." @default.
• W2118407113 created "2016-06-24" @default.
• W2118407113 creator A5007002927 @default.
• W2118407113 creator A5021419901 @default.
• W2118407113 creator A5045101008 @default.
• W2118407113 creator A5047713528 @default.
• W2118407113 creator A5055054082 @default.
• W2118407113 creator A5075947048 @default.
• W2118407113 creator A5078882754 @default.
• W2118407113 creator A5089525257 @default.
• W2118407113 creator A5091668678 @default.
• W2118407113 date "2013-12-15" @default.
• W2118407113 modified "2023-09-27" @default.
• W2118407113 title "Abstract P5-02-01: Regulated intratumoral expression of IL-12 in combination with cytotoxic agents as a strategy for the treatment of metastatic breast cancer" @default.
• W2118407113 doi "https://doi.org/10.1158/0008-5472.sabcs13-p5-02-01" @default.
• W2118407113 hasPublicationYear "2013" @default.
• W2118407113 type Work @default.
• W2118407113 sameAs 2118407113 @default.
• W2118407113 citedByCount "0" @default.
• W2118407113 crossrefType "proceedings-article" @default.
• W2118407113 hasAuthorship W2118407113A5007002927 @default.
• W2118407113 hasAuthorship W2118407113A5021419901 @default.
• W2118407113 hasAuthorship W2118407113A5045101008 @default.
• W2118407113 hasAuthorship W2118407113A5047713528 @default.
• W2118407113 hasAuthorship W2118407113A5055054082 @default.
• W2118407113 hasAuthorship W2118407113A5075947048 @default.
• W2118407113 hasAuthorship W2118407113A5078882754 @default.
• W2118407113 hasAuthorship W2118407113A5089525257 @default.
• W2118407113 hasAuthorship W2118407113A5091668678 @default.
• W2118407113 hasConcept C121608353 @default.
• W2118407113 hasConcept C126322002 @default.
• W2118407113 hasConcept C154317977 @default.
• W2118407113 hasConcept C202751555 @default.
• W2118407113 hasConcept C203014093 @default.
• W2118407113 hasConcept C2776187077 @default.
• W2118407113 hasConcept C2776390293 @default.
• W2118407113 hasConcept C502942594 @default.
• W2118407113 hasConcept C530470458 @default.
• W2118407113 hasConcept C55493867 @default.
• W2118407113 hasConcept C71924100 @default.
• W2118407113 hasConcept C86803240 @default.
• W2118407113 hasConcept C8891405 @default.
• W2118407113 hasConceptScore W2118407113C121608353 @default.
• W2118407113 hasConceptScore W2118407113C126322002 @default.
• W2118407113 hasConceptScore W2118407113C154317977 @default.
• W2118407113 hasConceptScore W2118407113C202751555 @default.
• W2118407113 hasConceptScore W2118407113C203014093 @default.
• W2118407113 hasConceptScore W2118407113C2776187077 @default.
• W2118407113 hasConceptScore W2118407113C2776390293 @default.
• W2118407113 hasConceptScore W2118407113C502942594 @default.
• W2118407113 hasConceptScore W2118407113C530470458 @default.
• W2118407113 hasConceptScore W2118407113C55493867 @default.
• W2118407113 hasConceptScore W2118407113C71924100 @default.
• W2118407113 hasConceptScore W2118407113C86803240 @default.
• W2118407113 hasConceptScore W2118407113C8891405 @default.
• W2118407113 hasLocation W21184071131 @default.
• W2118407113 hasOpenAccess W2118407113 @default.
• W2118407113 hasPrimaryLocation W21184071131 @default.
• W2118407113 hasRelatedWork W1184050512 @default.
• W2118407113 hasRelatedWork W1595688879 @default.
• W2118407113 hasRelatedWork W1994295187 @default.
• W2118407113 hasRelatedWork W2000044868 @default.
• W2118407113 hasRelatedWork W2034557574 @default.
• W2118407113 hasRelatedWork W2076141885 @default.
• W2118407113 hasRelatedWork W2124522062 @default.
• W2118407113 hasRelatedWork W2315450612 @default.
• W2118407113 hasRelatedWork W2326778442 @default.
• W2118407113 hasRelatedWork W2468131549 @default.
• W2118407113 hasRelatedWork W2469129484 @default.
• W2118407113 hasRelatedWork W2535172734 @default.
• W2118407113 hasRelatedWork W2750583332 @default.
• W2118407113 hasRelatedWork W2810528523 @default.
• W2118407113 hasRelatedWork W2953688059 @default.
• W2118407113 hasRelatedWork W2983325711 @default.
• W2118407113 hasRelatedWork W3083071627 @default.
• W2118407113 hasRelatedWork W3083291045 @default.
• W2118407113 hasRelatedWork W3104964377 @default.
• W2118407113 hasRelatedWork W597322156 @default.
• W2118407113 isParatext "false" @default.
• W2118407113 isRetracted "false" @default.
• W2118407113 magId "2118407113" @default.
• W2118407113 workType "article" @default.