Induction of robust type-1 CD8+ T-cell responses in WHO grade II low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC
Identifieur interne : 002712 ( Main/Exploration ); précédent : 002711; suivant : 002713Induction of robust type-1 CD8+ T-cell responses in WHO grade II low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC
Auteurs : Hideho Okada ; Lisa H. Butterfield ; Ronald L. Hamilton ; Aki Hoji ; Masashi Sakaki ; Brian J. Ahn ; Gary Kohanbash ; Jan Drappatz ; Johnathan Engh ; Nduka Amankulor ; Mark O. Lively [États-Unis] ; Michael D. Chan [États-Unis] ; Andres M. Salazar ; Edward G. Shaw [États-Unis] ; Douglas M. Potter [États-Unis] ; Frank S. LiebermanSource :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Antigènes néoplasiques (administration et posologie), Carboxyméthylcellulose de sodium (administration et posologie), Carboxyméthylcellulose de sodium (analogues et dérivés), Femelle, Gliome (anatomopathologie), Gliome (immunologie), Gliome (mortalité), Gliome (traitement médicamenteux), Grading des tumeurs, Humains, Lymphocytes T CD8+ (), Lymphocytes T CD8+ (immunologie), Mâle, Poly I-C (administration et posologie), Polylysine (administration et posologie), Polylysine (analogues et dérivés), Projets pilotes, Protocoles de polychimiothérapie antinéoplasique (pharmacologie), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Résultat thérapeutique, Survie sans rechute, Vaccins anticancéreux (administration et posologie), Vaccins sous-unitaires (administration et posologie).
- MESH :
- administration et posologie : Antigènes néoplasiques, Carboxyméthylcellulose de sodium, Poly I-C, Polylysine, Vaccins anticancéreux, Vaccins sous-unitaires.
- analogues et dérivés : Carboxyméthylcellulose de sodium, Polylysine.
- anatomopathologie : Gliome.
- immunologie : Gliome, Lymphocytes T CD8+.
- mortalité : Gliome.
- pharmacologie : Protocoles de polychimiothérapie antinéoplasique.
- traitement médicamenteux : Gliome.
- usage thérapeutique : Protocoles de polychimiothérapie antinéoplasique.
- Adulte, Adulte d'âge moyen, Femelle, Grading des tumeurs, Humains, Lymphocytes T CD8+, Mâle, Projets pilotes, Résultat thérapeutique, Survie sans rechute.
English descriptors
- KwdEn :
- Adult, Antigens, Neoplasm (administration & dosage), Antineoplastic Combined Chemotherapy Protocols (pharmacology), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), CD8-Positive T-Lymphocytes (drug effects), CD8-Positive T-Lymphocytes (immunology), Cancer Vaccines (administration & dosage), Carboxymethylcellulose Sodium (administration & dosage), Carboxymethylcellulose Sodium (analogs & derivatives), Disease-Free Survival, Female, Glioma (drug therapy), Glioma (immunology), Glioma (mortality), Glioma (pathology), Humans, Male, Middle Aged, Neoplasm Grading, Pilot Projects, Poly I-C (administration & dosage), Polylysine (administration & dosage), Polylysine (analogs & derivatives), Treatment Outcome, Vaccines, Subunit (administration & dosage).
- MESH :
- chemical , administration & dosage : Antigens, Neoplasm, Cancer Vaccines, Carboxymethylcellulose Sodium, Poly I-C, Polylysine, Vaccines, Subunit.
- chemical , analogs & derivatives : Carboxymethylcellulose Sodium, Polylysine.
- drug effects : CD8-Positive T-Lymphocytes.
- drug therapy : Glioma.
- immunology : CD8-Positive T-Lymphocytes, Glioma.
- mortality : Glioma.
- pathology : Glioma.
- pharmacology : Antineoplastic Combined Chemotherapy Protocols.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Adult, Disease-Free Survival, Female, Humans, Male, Middle Aged, Neoplasm Grading, Pilot Projects, Treatment Outcome.
Abstract
WHO grade II low-grade gliomas (LGGs) with high risk factors for recurrence are mostly lethal despite current treatments. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in HLA-A2+ adults with high-risk LGGs in the following three cohorts: 1) patients without prior progression, chemotherapy or radiation therapy (RT); 2) patients without prior progression or chemotherapy but with prior RT, and 3) recurrent patients.
GAAs were IL-13Rα2, EphA2, WT1, and Survivin. Synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for 8 courses with intramuscular injections of poly-ICLC, followed by q12week booster vaccines.
Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity was encountered except for one case with Grade 3 fever, fatigue and mood disturbance (Cohort 1). ELISPOT assays demonstrated robust IFN-γ responses against at least 3 of the 4 GAA epitopes in 10 and 4 cases of Cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFN-γ responses than Cohort 3 patients. Median progression-free survival (PFS) periods since the 1st vaccine are 17 months in Cohort 1 (range 10–47+) and 12 months in Cohort 3 (range 3–41+). The only patient with large astrocytoma in Cohort 2 has been progression-free for over 67 months since diagnosis.
The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade II glioma patients. These results warrant further evaluations of this approach.
Url:
DOI: 10.1158/1078-0432.CCR-14-1790
PubMed: 25424847
PubMed Central: 4297523
Affiliations:
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Le document en format XML
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Butterfield</name><affiliation><nlm:aff id="A4">Department of Medicine, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation><affiliation><nlm:aff id="A5">Department of Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation><affiliation><nlm:aff id="A8">Department of Immunology, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Hamilton, Ronald L" sort="Hamilton, Ronald L" uniqKey="Hamilton R" first="Ronald L." last="Hamilton">Ronald L. Hamilton</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A7">Department of Pathology, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Hoji, Aki" sort="Hoji, Aki" uniqKey="Hoji A" first="Aki" last="Hoji">Aki Hoji</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Sakaki, Masashi" sort="Sakaki, Masashi" uniqKey="Sakaki M" first="Masashi" last="Sakaki">Masashi Sakaki</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Ahn, Brian J" sort="Ahn, Brian J" uniqKey="Ahn B" first="Brian J." last="Ahn">Brian J. Ahn</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A8">Department of Immunology, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Kohanbash, Gary" sort="Kohanbash, Gary" uniqKey="Kohanbash G" first="Gary" last="Kohanbash">Gary Kohanbash</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Drappatz, Jan" sort="Drappatz, Jan" uniqKey="Drappatz J" first="Jan" last="Drappatz">Jan Drappatz</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation><affiliation><nlm:aff id="A6">Department of Neurology, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Engh, Johnathan" sort="Engh, Johnathan" uniqKey="Engh J" first="Johnathan" last="Engh">Johnathan Engh</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Amankulor, Nduka" sort="Amankulor, Nduka" uniqKey="Amankulor N" first="Nduka" last="Amankulor">Nduka Amankulor</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author><author><name sortKey="Lively, Mark O" sort="Lively, Mark O" uniqKey="Lively M" first="Mark O." last="Lively">Mark O. Lively</name><affiliation wicri:level="2"><nlm:aff id="A11">Wake Forest University School of Medicine, Winston-Salem, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Wake Forest University School of Medicine, Winston-Salem</wicri:cityArea></affiliation></author><author><name sortKey="Chan, Michael D" sort="Chan, Michael D" uniqKey="Chan M" first="Michael D." last="Chan">Michael D. Chan</name><affiliation wicri:level="2"><nlm:aff id="A11">Wake Forest University School of Medicine, Winston-Salem, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Wake Forest University School of Medicine, Winston-Salem</wicri:cityArea></affiliation></author><author><name sortKey="Salazar, Andres M" sort="Salazar, Andres M" uniqKey="Salazar A" first="Andres M." last="Salazar">Andres M. Salazar</name><affiliation><nlm:aff id="A12">Oncovir, Inc.</nlm:aff><wicri:noCountry code="subfield">Inc.</wicri:noCountry></affiliation></author><author><name sortKey="Shaw, Edward G" sort="Shaw, Edward G" uniqKey="Shaw E" first="Edward G." last="Shaw">Edward G. Shaw</name><affiliation wicri:level="2"><nlm:aff id="A11">Wake Forest University School of Medicine, Winston-Salem, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Wake Forest University School of Medicine, Winston-Salem</wicri:cityArea></affiliation></author><author><name sortKey="Potter, Douglas M" sort="Potter, Douglas M" uniqKey="Potter D" first="Douglas M." last="Potter">Douglas M. Potter</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation wicri:level="4"><nlm:aff id="A9">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh</nlm:aff><country>États-Unis</country><placeName><settlement type="city">Pittsburgh</settlement><region type="state">Pennsylvanie</region></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Lieberman, Frank S" sort="Lieberman, Frank S" uniqKey="Lieberman F" first="Frank S." last="Lieberman">Frank S. Lieberman</name><affiliation><nlm:aff id="A1">Brain Tumor Program, University of Pittsburgh Cancer Institute (UPCI)</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh Cancer Institute (UPCI)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A3">Department of Neurological Surgery, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation><affiliation><nlm:aff id="A6">Department of Neurology, University of Pittsburgh School of Medicine</nlm:aff><wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry></affiliation></author></analytic><series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title><idno type="ISSN">1078-0432</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Antigens, Neoplasm (administration & dosage)</term><term>Antineoplastic Combined Chemotherapy Protocols (pharmacology)</term><term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term><term>CD8-Positive T-Lymphocytes (drug effects)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cancer Vaccines (administration & dosage)</term><term>Carboxymethylcellulose Sodium (administration & dosage)</term><term>Carboxymethylcellulose Sodium (analogs & derivatives)</term><term>Disease-Free Survival</term><term>Female</term><term>Glioma (drug therapy)</term><term>Glioma (immunology)</term><term>Glioma (mortality)</term><term>Glioma (pathology)</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neoplasm Grading</term><term>Pilot Projects</term><term>Poly I-C (administration & dosage)</term><term>Polylysine (administration & dosage)</term><term>Polylysine (analogs & derivatives)</term><term>Treatment Outcome</term><term>Vaccines, Subunit (administration & dosage)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Antigènes néoplasiques (administration et posologie)</term><term>Carboxyméthylcellulose de sodium (administration et posologie)</term><term>Carboxyméthylcellulose de sodium (analogues et dérivés)</term><term>Femelle</term><term>Gliome (anatomopathologie)</term><term>Gliome (immunologie)</term><term>Gliome (mortalité)</term><term>Gliome (traitement médicamenteux)</term><term>Grading des tumeurs</term><term>Humains</term><term>Lymphocytes T CD8+ ()</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Mâle</term><term>Poly I-C (administration et posologie)</term><term>Polylysine (administration et posologie)</term><term>Polylysine (analogues et dérivés)</term><term>Projets pilotes</term><term>Protocoles de polychimiothérapie antinéoplasique (pharmacologie)</term><term>Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique)</term><term>Résultat thérapeutique</term><term>Survie sans rechute</term><term>Vaccins anticancéreux (administration et posologie)</term><term>Vaccins sous-unitaires (administration et posologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antigens, Neoplasm</term><term>Cancer Vaccines</term><term>Carboxymethylcellulose Sodium</term><term>Poly I-C</term><term>Polylysine</term><term>Vaccines, Subunit</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Carboxymethylcellulose Sodium</term><term>Polylysine</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antigènes néoplasiques</term><term>Carboxyméthylcellulose de sodium</term><term>Poly I-C</term><term>Polylysine</term><term>Vaccins anticancéreux</term><term>Vaccins sous-unitaires</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Carboxyméthylcellulose de sodium</term><term>Polylysine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Gliome</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Gliome</term><term>Lymphocytes T CD8+</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Gliome</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Protocoles de polychimiothérapie antinéoplasique</term></keywords><keywords scheme="MESH" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Gliome</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Protocoles de polychimiothérapie antinéoplasique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Disease-Free Survival</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neoplasm Grading</term><term>Pilot Projects</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Femelle</term><term>Grading des tumeurs</term><term>Humains</term><term>Lymphocytes T CD8+</term><term>Mâle</term><term>Projets pilotes</term><term>Résultat thérapeutique</term><term>Survie sans rechute</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>PURPOSE</title><p id="P1">WHO grade II low-grade gliomas (LGGs) with high risk factors for recurrence are mostly lethal despite current treatments. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in HLA-A2<sup>+</sup> adults with high-risk LGGs in the following three cohorts: 1) patients without prior progression, chemotherapy or radiation therapy (RT); 2) patients without prior progression or chemotherapy but with prior RT, and 3) recurrent patients.</p></sec><sec id="S2"><title>METHODS</title><p id="P2">GAAs were IL-13Rα2, EphA2, WT1, and Survivin. Synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for 8 courses with intramuscular injections of poly-ICLC, followed by q12week booster vaccines.</p></sec><sec id="S3"><title>RESULTS</title><p id="P3">Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity was encountered except for one case with Grade 3 fever, fatigue and mood disturbance (Cohort 1). ELISPOT assays demonstrated robust IFN-γ responses against at least 3 of the 4 GAA epitopes in 10 and 4 cases of Cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFN-γ responses than Cohort 3 patients. Median progression-free survival (PFS) periods since the 1<sup>st</sup> vaccine are 17 months in Cohort 1 (range 10–47+) and 12 months in Cohort 3 (range 3–41+). The only patient with large astrocytoma in Cohort 2 has been progression-free for over 67 months since diagnosis.</p></sec><sec id="S4"><title>CONCLUSION</title><p id="P4">The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade II glioma patients. These results warrant further evaluations of this approach.</p></sec></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><noCountry><name sortKey="Ahn, Brian J" sort="Ahn, Brian J" uniqKey="Ahn B" first="Brian J." last="Ahn">Brian J. Ahn</name><name sortKey="Amankulor, Nduka" sort="Amankulor, Nduka" uniqKey="Amankulor N" first="Nduka" last="Amankulor">Nduka Amankulor</name><name sortKey="Butterfield, Lisa H" sort="Butterfield, Lisa H" uniqKey="Butterfield L" first="Lisa H." last="Butterfield">Lisa H. Butterfield</name><name sortKey="Drappatz, Jan" sort="Drappatz, Jan" uniqKey="Drappatz J" first="Jan" last="Drappatz">Jan Drappatz</name><name sortKey="Engh, Johnathan" sort="Engh, Johnathan" uniqKey="Engh J" first="Johnathan" last="Engh">Johnathan Engh</name><name sortKey="Hamilton, Ronald L" sort="Hamilton, Ronald L" uniqKey="Hamilton R" first="Ronald L." last="Hamilton">Ronald L. Hamilton</name><name sortKey="Hoji, Aki" sort="Hoji, Aki" uniqKey="Hoji A" first="Aki" last="Hoji">Aki Hoji</name><name sortKey="Kohanbash, Gary" sort="Kohanbash, Gary" uniqKey="Kohanbash G" first="Gary" last="Kohanbash">Gary Kohanbash</name><name sortKey="Lieberman, Frank S" sort="Lieberman, Frank S" uniqKey="Lieberman F" first="Frank S." last="Lieberman">Frank S. Lieberman</name><name sortKey="Okada, Hideho" sort="Okada, Hideho" uniqKey="Okada H" first="Hideho" last="Okada">Hideho Okada</name><name sortKey="Sakaki, Masashi" sort="Sakaki, Masashi" uniqKey="Sakaki M" first="Masashi" last="Sakaki">Masashi Sakaki</name><name sortKey="Salazar, Andres M" sort="Salazar, Andres M" uniqKey="Salazar A" first="Andres M." last="Salazar">Andres M. Salazar</name></noCountry><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Lively, Mark O" sort="Lively, Mark O" uniqKey="Lively M" first="Mark O." last="Lively">Mark O. Lively</name></region><name sortKey="Chan, Michael D" sort="Chan, Michael D" uniqKey="Chan M" first="Michael D." last="Chan">Michael D. Chan</name><name sortKey="Potter, Douglas M" sort="Potter, Douglas M" uniqKey="Potter D" first="Douglas M." last="Potter">Douglas M. Potter</name><name sortKey="Shaw, Edward G" sort="Shaw, Edward G" uniqKey="Shaw E" first="Edward G." last="Shaw">Edward G. Shaw</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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