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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-2-22
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pubmed:abstractText |
Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a survival benefit in GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) (200 mg/m(2) per 5 days) or dose-intensified (DI) TMZ (100 mg/m(2) per 21 days). All patients receiving STD TMZ exhibited at least a transient grade 2 lymphopenia, whereas those receiving DI TMZ exhibited a sustained grade 3 lymphopenia (<500 cells/?L). CD3(+) T-cell (P = .005) and B-cell (P = .004) counts were reduced significantly only in the DI cohort. Patients in the DI cohort had an increase in the proportion of immunosuppressive regulatory T cells (T(Reg); P = .008). EGFRvIII-specific immune responses developed in all patients treated with either regimen, but the DI TMZ regimen produced humoral (P = .037) and delayed-type hypersensitivity responses (P = .036) of greater magnitude. EGFRvIII-expressing tumor cells were also eradicated in nearly all patients (91.6%; CI(95): 64.0%-99.8%; P < .0001). The median progression-free survival (15.2 months; CI(95): 11.0-18.5 months; hazard ratio [HR] = 0.35; P = .024) and overall survival (23.6 months; CI(95): 18.5-33.1 months; HR = 0.23; P = .019) exceeded those of historical controls matched for entry criteria and adjusted for known prognostic factors. EGFRvIII-targeted vaccination induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFRvIII-expressing tumor cells without autoimmunity.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/1R25-NS065731-01,
http://linkedlifedata.com/resource/pubmed/grant/3R01-CA135272-02S1,
http://linkedlifedata.com/resource/pubmed/grant/3R21CA132891-02S1,
http://linkedlifedata.com/resource/pubmed/grant/5P50-CA108786-05,
http://linkedlifedata.com/resource/pubmed/grant/5P50-NS020023-26,
http://linkedlifedata.com/resource/pubmed/grant/5R01-CA135272-02,
http://linkedlifedata.com/resource/pubmed/grant/5R21-CA132891-02,
http://linkedlifedata.com/resource/pubmed/grant/P50-CA108786,
http://linkedlifedata.com/resource/pubmed/grant/P50-CA108786-05,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA097611,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA1208113,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA97222-05,
http://linkedlifedata.com/resource/pubmed/grant/R37 CA011898
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1523-5866
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pubmed:author |
pubmed-author:AldapeKenneth DKD,
pubmed-author:ArcherGary EGE,
pubmed-author:BignerDarell DDD,
pubmed-author:CoanAprilA,
pubmed-author:DesjardinsAnnickA,
pubmed-author:FriedmanAllan HAH,
pubmed-author:FriedmanHenry SHS,
pubmed-author:GilbertMark RMR,
pubmed-author:HeimbergerAmy BAB,
pubmed-author:HerndonJames EJE,
pubmed-author:McLendonRoger ERE,
pubmed-author:MitchellDuane ADA,
pubmed-author:ReardonDavid ADA,
pubmed-author:SampsonJohn HJH,
pubmed-author:SawayaRaymondR,
pubmed-author:SchmittlingRobertR,
pubmed-author:ShiWeimingW,
pubmed-author:VredenburghJames JJJ
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pubmed:issnType |
Electronic
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
324-33
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pubmed:meshHeading |
pubmed-meshheading:21149254-Adult,
pubmed-meshheading:21149254-Aged,
pubmed-meshheading:21149254-Aged, 80 and over,
pubmed-meshheading:21149254-Antineoplastic Agents, Alkylating,
pubmed-meshheading:21149254-Brain Neoplasms,
pubmed-meshheading:21149254-Chemotherapy, Adjuvant,
pubmed-meshheading:21149254-Cohort Studies,
pubmed-meshheading:21149254-DNA Methylation,
pubmed-meshheading:21149254-Dacarbazine,
pubmed-meshheading:21149254-Female,
pubmed-meshheading:21149254-Glioblastoma,
pubmed-meshheading:21149254-Humans,
pubmed-meshheading:21149254-Hypersensitivity, Delayed,
pubmed-meshheading:21149254-Immunoenzyme Techniques,
pubmed-meshheading:21149254-Lymphopenia,
pubmed-meshheading:21149254-Male,
pubmed-meshheading:21149254-Middle Aged,
pubmed-meshheading:21149254-Mutation,
pubmed-meshheading:21149254-O(6)-Methylguanine-DNA Methyltransferase,
pubmed-meshheading:21149254-Receptor, Epidermal Growth Factor,
pubmed-meshheading:21149254-Survival Rate,
pubmed-meshheading:21149254-T-Lymphocytes,
pubmed-meshheading:21149254-T-Lymphocytes, Regulatory,
pubmed-meshheading:21149254-Treatment Outcome,
pubmed-meshheading:21149254-Vaccines, Subunit
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pubmed:year |
2011
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pubmed:articleTitle |
Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma.
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pubmed:affiliation |
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Multicenter Study,
Clinical Trial, Phase II,
Research Support, N.I.H., Extramural
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