e-Article
Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials.
Document Type
Academic Journal
Author
Cornetta K; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Brown Center for Immunotherapy, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: kcornett@iu.edu.; Yao J; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; House K; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Duffy L; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Adusumilli PS; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Beyer R; Surgery Branch, NCI, Bethesda, MD 20892, USA.; Booth C; Molecular and Cellular Immunology, UCL Great Ormond Street Institute of Child Health, London, UK.; Brenner M; Center for Cell and Gene Therapy Baylor College of Medicine, Houston TX, USA.; Curran K; Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY, USA; Weill Cornell Medical College, Department of Pediatrics, New York, NY, USA.; Grilley B; Center for Cell and Gene Therapy Baylor College of Medicine, Houston TX, USA.; Heslop H; Center for Cell and Gene Therapy Baylor College of Medicine, Houston TX, USA.; Hinrichs CS; Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence, New Brunswick, NJ 08901, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.; Kaplan RN; Pediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD 20892, USA.; Kiem HP; Fred Hutchison Cancer Center and University of Washington, Seattle, WA, USA.; Kochenderfer J; Center for Cancer Research, Surgery Branch, NCI, NIH, Bethesda MD, USA.; Kohn DB; Departments of Microbiology, Immunology and Molecular Genetics, Pediatrics (Hematology/Oncology) and Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.; Mailankody S; Myeloma and Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Norberg SM; NCI, Center for Immuno-Oncology, Bethesda, MD 20892, USA.; O'Cearbhaill RE; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Pappas J; Surgery Branch, NCI, Bethesda, MD 20892, USA.; Park J; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Ramos C; Center for Cell and Gene Therapy Baylor College of Medicine, Houston TX, USA.; Ribas A; Jonsson Comprehensive Cancer Center at the University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Rivière I; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Rosenberg SA; Surgery Branch, NCI, Bethesda, MD 20892, USA.; Sauter C; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.; Shah NN; Pediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD 20892, USA.; Slovin SF; Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Thrasher A; Molecular and Cellular Immunology, UCL Great Ormond Street Institute of Child Health, London, UK.; Williams DA; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Lin TY; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Brown Center for Immunotherapy, Indiana University School of Medicine, Indianapolis, IN, USA.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE
Subject
Language
English
Abstract
The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy.
Competing Interests: Declaration of interests Indiana University has licensed technology to Charles River Laboratories and Genezen Inc. based on unrelated work developed by K.Co., L.D., and T-Y. L., who each receive royalties. P.A.S receives research funding from ATARA Biotherapeutics; Scientific Advisory Board and Consultant: ATARA Biotherapeuticcs, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion, Outpace Bio; research funding and intellectual property licensed to ATARA Biotherapeutics. M.B. has equity in AlloVir, Marker Therapeutics, and Tessa Therapeutics; serves on the Scientific Advisory Board for Tessa Therapeutics, Marker Therapeutics, Allogene, Walking Fish, Cell Genix, Kuur, Turnstone Biologics, Posedia, Tscan, and Bluebird Bio; and receives royalities from Takeda and Bellicum. K.Cu. is a consultant to Novartis and receives research support from Novartis, Cellectis, and Celgene. B.G. has equity in AlloVir, QBRegulatory LLC, and QBRegulatory, and provides consulting services to AlloVir, Marker Therapeutics, Tessa Therapeutics, Lokon Pharma and Proxima Clinical Research. H.H. has equity in AlloVir and Marker Therapeutics, and serves on the Scientific Advisory Board for Gilead Biosciences, Novartis, Tessa Therapeutics, Marker Therapeutics, Kiadis, PACT Pharma, Mesoblast, and receives research support from Tessa Therapeutics and Kuur Therapeutics. C.S.H. performs consulting and advisory board services for Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, and PACT Pharma; patents and royalties for NIH patents in cell and gene therapy and immunotherapy; research funding from Neogene Therapeutics and T-Cure Biosciences. J.K. has research support and royalty from Kite, a Gilead Company; and receives research funding from Bristol-Myers Squibb, Royalties: Kyverna. D.B.K. is a paid Scientific Advisory Board member for Allogene Therapeutics, ImmunoVec, Pluto Therapeutics, MyoGene Bio, Innoskel and an ad hoc consultant for Cimeio Therapeutics, TransformaTx, and Bluebird Bio. S.M. receives research funding from Allogene Therapeutics, Takeda Oncology, Juno Therapeutics, Bristol-Myers Squibb, Janssen Oncology, Fate Therapeutics and serves on the advisory panel for Legend Biotech, Evicore, Janssen Oncology, BioAscend, Optum Oncology, and EcoR1; and receives honoraria from Plexus Communication, OncLive, Physician Education Resource. R.O. receives compensation from Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Gynecologic Oncology Foundation, Bayer, Curio/Onclive, R-Pharm, Immunogen, Hitech Health; non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies; non-compensated advisor for Carina Biotech. A.R. has received honoraria from consulting with Amgen, Bristol-Myers Squibb and Merck, is or has been a member of the scientific advisory board and holds stock in Advaxis, Appia, Apricity, Arcus, Compugen, CytomX, Highlight, ImaginAb, ImmPact, ImmuneSensor, Inspirna, Isoplexis, Kite-Gilead, Lutris, MapKure, Merus, PACT, Pluto, RAPT, Synthekine and Tango; and has received research funding from Agilent and from Bristol-Myers Squibb through Stand Up to Cancer (SU2C), and patent royalties from Arsenal Bio. C.R. is Scientific Board Member for Novartis; research support from Tessa Therapeutics and Kuur Therapeutics. I.R. has equity or property rights with FloDesign Sonics, Takeda Pharmaceuticals, Fate Therapeutics, Mnemo Therapeutics, Juno Therapeutics; Services and Travel: Center for Commercialization of Cancer, Akron. C.S. is a consultant for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/a Gilead Company, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, Ono Pharmaceuticals, MorphoSys, CSL Behring, Syncopation Life Sciences, CRISPR Therapeutics, and GSK; research funds: Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, Actinium Pharmaceuticals and Sanofi-Genzyme. S.S.: research funding: Sanofi-Aventis, Poseida Pharmaceuticals, Gilead Sciences, Inc, Prostate Cancer Foundation; Honoraria: Physician Education Resources, Janssen, Pfizer, Tolmar. D.A.W. holds intellectual property rights to the vector utilized in the trial reported in this manuscript.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests Indiana University has licensed technology to Charles River Laboratories and Genezen Inc. based on unrelated work developed by K.Co., L.D., and T-Y. L., who each receive royalties. P.A.S receives research funding from ATARA Biotherapeutics; Scientific Advisory Board and Consultant: ATARA Biotherapeuticcs, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion, Outpace Bio; research funding and intellectual property licensed to ATARA Biotherapeutics. M.B. has equity in AlloVir, Marker Therapeutics, and Tessa Therapeutics; serves on the Scientific Advisory Board for Tessa Therapeutics, Marker Therapeutics, Allogene, Walking Fish, Cell Genix, Kuur, Turnstone Biologics, Posedia, Tscan, and Bluebird Bio; and receives royalities from Takeda and Bellicum. K.Cu. is a consultant to Novartis and receives research support from Novartis, Cellectis, and Celgene. B.G. has equity in AlloVir, QBRegulatory LLC, and QBRegulatory, and provides consulting services to AlloVir, Marker Therapeutics, Tessa Therapeutics, Lokon Pharma and Proxima Clinical Research. H.H. has equity in AlloVir and Marker Therapeutics, and serves on the Scientific Advisory Board for Gilead Biosciences, Novartis, Tessa Therapeutics, Marker Therapeutics, Kiadis, PACT Pharma, Mesoblast, and receives research support from Tessa Therapeutics and Kuur Therapeutics. C.S.H. performs consulting and advisory board services for Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, and PACT Pharma; patents and royalties for NIH patents in cell and gene therapy and immunotherapy; research funding from Neogene Therapeutics and T-Cure Biosciences. J.K. has research support and royalty from Kite, a Gilead Company; and receives research funding from Bristol-Myers Squibb, Royalties: Kyverna. D.B.K. is a paid Scientific Advisory Board member for Allogene Therapeutics, ImmunoVec, Pluto Therapeutics, MyoGene Bio, Innoskel and an ad hoc consultant for Cimeio Therapeutics, TransformaTx, and Bluebird Bio. S.M. receives research funding from Allogene Therapeutics, Takeda Oncology, Juno Therapeutics, Bristol-Myers Squibb, Janssen Oncology, Fate Therapeutics and serves on the advisory panel for Legend Biotech, Evicore, Janssen Oncology, BioAscend, Optum Oncology, and EcoR1; and receives honoraria from Plexus Communication, OncLive, Physician Education Resource. R.O. receives compensation from Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Gynecologic Oncology Foundation, Bayer, Curio/Onclive, R-Pharm, Immunogen, Hitech Health; non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies; non-compensated advisor for Carina Biotech. A.R. has received honoraria from consulting with Amgen, Bristol-Myers Squibb and Merck, is or has been a member of the scientific advisory board and holds stock in Advaxis, Appia, Apricity, Arcus, Compugen, CytomX, Highlight, ImaginAb, ImmPact, ImmuneSensor, Inspirna, Isoplexis, Kite-Gilead, Lutris, MapKure, Merus, PACT, Pluto, RAPT, Synthekine and Tango; and has received research funding from Agilent and from Bristol-Myers Squibb through Stand Up to Cancer (SU2C), and patent royalties from Arsenal Bio. C.R. is Scientific Board Member for Novartis; research support from Tessa Therapeutics and Kuur Therapeutics. I.R. has equity or property rights with FloDesign Sonics, Takeda Pharmaceuticals, Fate Therapeutics, Mnemo Therapeutics, Juno Therapeutics; Services and Travel: Center for Commercialization of Cancer, Akron. C.S. is a consultant for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/a Gilead Company, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, Ono Pharmaceuticals, MorphoSys, CSL Behring, Syncopation Life Sciences, CRISPR Therapeutics, and GSK; research funds: Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, Actinium Pharmaceuticals and Sanofi-Genzyme. S.S.: research funding: Sanofi-Aventis, Poseida Pharmaceuticals, Gilead Sciences, Inc, Prostate Cancer Foundation; Honoraria: Physician Education Resources, Janssen, Pfizer, Tolmar. D.A.W. holds intellectual property rights to the vector utilized in the trial reported in this manuscript.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)