NDLI: FIRST-IN-HUMAN PHASE I CLINICAL TRIAL OF ONCOLYTIC DELTA-24-RGD (DNX-2401) WITH BIOLOGICAL ENDPOINTS: IMPLICATIONS FOR VIRO- IMMUNOTHERAPY

Content Provider	PubMed Central
Author	Lang, Frederick F. Conrad, Charles Gomez Manzano, Cande Tufaro, Frank Yung, Wka Sawaya, Raymond Weinberg, Jeffrey Prabhu, Sujit Fuller, Gregory Aldape, Kenneth Fueyo, Juan
Copyright Year	2014
Abstract	BACKGROUND: (blind field). METHODS: Patients with recurrent high grade gliomas were enrolled in one of two arms. Group A patients (clinical assessment group) received a single intratumoral injection of DNX-2401 into biopsy-proven recurrent glioma. Group B patients (biological endpoint group) received an initial intratumoral injection through a permanently implanted catheter (to identify the injection site) followed 14 days later by en bloc tumor resection (to obtain post-treatment specimens) and subsequent injection of DNX-2401 into the post-resection tumor bed. Dose was escalated from 1x10^7 to 3x10^10 viral particles (vp) in 8 cohorts. Patients were followed with clinical exams, MRIs, and laboratory studies. RESULTS: Histological analysis of post-treatment en bloc surgical specimens cut perpendicular to the implanted catheter proved for the first time that DNX-2401 was capable of infecting, replicating in, and killing human glioma tumor cells (Group B; N = 12). The maximum dose achieved was 3 × 10^10 vp as planned (Group A; N = 25). DNX-2401 resulted in no toxicity in each cohort. Ongoing outcome analyses show an overall median survival of 11 months. Remarkably, complete responses were seen in 3 patients (12%) (#12, #33, #37), all of whom are currently alive with no evidence of disease (3.2, 2 and 1.75 years after treatment). Serial MRIs revealed a period of increased enhancement prior to tumor regression, consistent with an inflammatory response. Histological analysis of a resected tumor from a symptomatic patient (#20) in Arm A during this period of increased MRI-enhancement identified primarily inflammatory cells (macrophages/CD8 T-cells) and only rare glioma cells. Analyses of inflammatory cytokines in serum revealed that, compared with all other patients, the 3 responders had 10-fold to 10,000-fold increases in Interleukin-12p70 (which polarizes T(h)0-cells to T(h)1-cells and promotes cell-mediated immunity). CONCLUSIONS: DNX-2401 is a new oncolytic virus with a favorable toxicity profile that is capable of replicating in and killing human glioma cells. Efficacy in this early stage trial was impressive with a 12% complete response-rate that has proven to be durable. Molecular studies suggest that viral-induced, anti-tumor cytotoxic immunity (in situ vaccine) may play a role in the anti-glioma effect of DNX-2401. SECONDARY CATEGORY: Immunobiology & Immunotherapy.
Related Links	http://dx.doi.org/10.1093/neuonc/nou208.61
Starting Page	39
File Format	PDF
ISSN	15228517
e-ISSN	15235866
Journal	Neuro-Oncology
Issue Number	Suppl 3
Volume Number	16
Language	English
Publisher	Oxford University Press
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Cancer Research Oncology Clinical Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Neurology (clinical) Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

NT-18PHASE I CLINICAL TRIAL OF ONCOLYTIC VIRUS DELTA-24-RGD (DNX-2401) WITH BIOLOGICAL ENDPOINTS: IMPLICATIONS FOR VIRO-IMMUNOTHERAPY

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report

Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors

GITRL-armed Delta-24-RGD oncolytic adenovirus prolongs survival and induces anti-glioma immune memory

Human Bone Marrow-Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Delta-24-RGD to Human Gliomas

P12A PHASE I TRIAL OF INTRAVENOUS ONCOLYTIC REOLYSIN® IN PATIENTS WITH BRAIN TUMOURS

ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN RECURRENT GLIOBLASTOMA (GBM): FIRST PHASE I CLINICAL TRIAL EVALUATING THE INTRATUMORAL ADMINISTRATION

HGG-15. THE IMIPRIDONE ONC201 IN COMBINATION WITH THE ONCOLYTIC ADENOVIRUS DELTA-24-RGD HAS A SYNERGISTIC EFFECT IN PRECLINICAL MODELS OF PHGGS AND DMGS

Rewiring cancer cell death to enhance oncolytic viro-immunotherapy

FIRST-IN-HUMAN PHASE I CLINICAL TRIAL OF ONCOLYTIC DELTA-24-RGD (DNX-2401) WITH BIOLOGICAL ENDPOINTS: IMPLICATIONS FOR VIRO- IMMUNOTHERAPY

Similar Documents

NT-18PHASE I CLINICAL TRIAL OF ONCOLYTIC VIRUS DELTA-24-RGD (DNX-2401) WITH BIOLOGICAL ENDPOINTS: IMPLICATIONS FOR VIRO-IMMUNOTHERAPY

DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report

Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors

GITRL-armed Delta-24-RGD oncolytic adenovirus prolongs survival and induces anti-glioma immune memory

Human Bone Marrow-Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Delta-24-RGD to Human Gliomas

P12A PHASE I TRIAL OF INTRAVENOUS ONCOLYTIC REOLYSIN® IN PATIENTS WITH BRAIN TUMOURS

ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN RECURRENT GLIOBLASTOMA (GBM): FIRST PHASE I CLINICAL TRIAL EVALUATING THE INTRATUMORAL ADMINISTRATION

HGG-15. THE IMIPRIDONE ONC201 IN COMBINATION WITH THE ONCOLYTIC ADENOVIRUS DELTA-24-RGD HAS A SYNERGISTIC EFFECT IN PRECLINICAL MODELS OF PHGGS AND DMGS

Rewiring cancer cell death to enhance oncolytic viro-immunotherapy

FIRST-IN-HUMAN PHASE I CLINICAL TRIAL OF ONCOLYTIC DELTA-24-RGD (DNX-2401) WITH BIOLOGICAL ENDPOINTS: IMPLICATIONS FOR VIRO- IMMUNOTHERAPY