Evidence map›Paper›PMID 26843484›Full record

Trial reportNeuro-oncology2016

Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.

Lee A Wheeler, Andrea G Manzanera, Susan D Bell, Robert Cavaliere, John M McGregor, John C Grecula, Herbert B Newton, Simon S Lo, Behnam Badie, Jana Portnow and 7 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00589875 (A Phase IIa Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas), which is not on this map. Cited by 114 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 9 pooled it
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00589875 phase2completednot on this map

A Phase IIa Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas

TypeinterventionalSponsorCandel Therapeutics, Inc.Ran2007 to 2016Enrolled52ConditionsMalignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma, High Grade GliomaArmsCAN-2409, Valacyclovir, Temozolomide, Radiation therapy
3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 9 syntheses or guidelines pooled it, 166 citations in OpenAlex.

  1. Pooled it
  2. A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Pooled it
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  7. Clinical Application of Oncolytic Viruses: A Systematic Review.International journal of molecular sciences · 2020
    Pooled it
  8. Pooled it
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  10. [Intraprostatic gene therapy with aglatimagene as an adjunct to radiotherapy].Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026
    Article
  11. Review
  12. Review
  13. Observational
  14. The emerging role of oncolytic virotherapy in genitourinary malignancies.Frontiers in cell and developmental biology · 2026
    Review
  15. Immunotherapy in central nervous system tumors.International journal of surgery (London, England) · 2025
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 1 country.

Lee A WheelerBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Andrea G ManzaneraBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Susan D BellBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Robert CavaliereBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
John M McGregorBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
John C GreculaBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Herbert B NewtonBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Simon S LoBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Behnam BadieBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Jana PortnowBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Bin S TehBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Todd W TraskBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
David S BaskinBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Pamela Z NewBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Laura K AguilarBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Estuardo Aguilar-CordovaBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
E Antonio ChioccaBrigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).
Harvard University · USBrigham and Women's Hospital · USAdvantagene (United States) · USCity of Hope · USCase Western Reserve University · USMethodist Hospital · USUniversity Hospitals Seidman Cancer Center · US

Funding

The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHIOCCA, E. ANTONIO · 1996 to 2021
$30.9M
Clinical study of AdV-tk radiogene therapy for malignant gliomaR44CA107745 · NCI · ADVANTAGENE, INC · PI AGUILAR-CORDOVA, ESTUARDO · 2004 to 2009
$2.9M
NCI NIH HHS P01 CA069246NCI NIH HHS R44 CA107745
6 · The paper itself

Abstract

backgroundDespite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This Phase II, prospective, matched controlled, multicenter trial was conducted to assess the safety and efficacy of aglatimagene besadenovec (AdV-tk) plus valacyclovir (gene-mediated cytotoxic immunotherapy [GMCI]) in combination with SOC for newly diagnosed malignant glioma patients.

methodsTreatment cohort patients received SOC + GMCI and were enrolled at 4 institutions from 2006 to 2010. The preplanned, matched-control cohort included all concurrent patients meeting protocol criteria and SOC at a fifth institution. AdV-tk was administered at surgery followed by SOC radiation and temozolomide. Subset analyses were preplanned, based on prognostic factors: pathological diagnosis (glioblastoma vs others) and extent of resection.

resultsForty-eight patients completed SOC + GMCI, and 134 met control cohort criteria. Median overall survival (OS) was 17.1 months for GMCI + SOC versus 13.5 months for SOC alone (P = .0417). Survival at 1, 2, and 3 years was 67%, 35%, and 19% versus 57%, 22%, and 8%, respectively. The greatest benefit was observed in gross total resection patients: median OS of 25 versus 16.9 months (P = .0492); 1, 2, and 3-year survival of 90%, 53%, and 32% versus 64%, 28% and 6%, respectively. There were no dose-limiting toxicities; fever, fatigue, and headache were the most common GMCI-related symptoms.

conclusionsGMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival outcomes were most notably improved in patients with minimal residual disease after gross total resection. These data should help guide future immunotherapy studies and strongly support further evaluation of GMCI for malignant gliomas. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov NCT00589875.

Indexed as

AcyclovirAdenoviridaeAdultAgedAntiviral AgentsBrain NeoplasmsChemotherapy, AdjuvantGenetic TherapyGenetic VectorsGliomaHumansImmunotherapyMiddle AgedSimplexvirusSurvival AnalysisThymidine KinaseAcyclovirAntiviral AgentsThymidine KinaseValacyclovirValinegene therapyglioblastomaimmuno-oncologyimmunotherapymalignant glioma

Identifiers

PMID26843484
PMCPMC4933478
OpenAlexW2304124491

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.