Clinical development of retroviral replicating vector Toca 511 for gene therapy of cancer

References

• World Cancer Report: Cancer Research for Cancer Prevention. Wild, CP, Weiderpass E, Stewart, BW. World Health Organization/International Agency for Research on Cancer (IARC) Publications; Lyon, France. 2020.
   Google Scholar
• Edelstein, ML, Abedi MR, Wixon J, et al. Gene Therapy Clinical Trials Worldwide 1989-2004 - an overview. J Gene Med. 2004;6(6):597-602. DOI: https://doi.org/10.1002/jgm.619
   Google Scholar
• Rainov NG, Ren H. Clinical trials with retrovirus mediated gene therapy–what have we learned? J Neurooncol. 2003;65(3):227–236. DOI:https://doi.org/10.1023/B:NEON.0000003652.71665.f2
   Google Scholar
• Lang FF, Bruner JM, Fuller GN, et al. Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol. 2003;21(13):2508–2518. DOI:https://doi.org/10.1200/JCO.2003.21.13.2508
   Google Scholar
• Harrington KJ, Vile RG, Melcher A, et al. Clinical trials with oncolytic reovirus: moving beyond phase I into combinations with standard therapeutics. Cytokine Growth Factor Rev. 2010;21(2-3):91–98. DOI:https://doi.org/10.1016/j.cytogfr.2010.02.006
   Google Scholar
• Gomez-Manzano C, Fueyo J. Oncolytic adenoviruses for the treatment of brain tumors. Curr Opin Mol Ther. 2010;12(5):530–537.
   PubMedGoogle Scholar
• Russell SJ, Peng KW. Measles virus for cancer therapy. Curr Top Microbiol Immunol. 2009;330(213–241). DOI:https://doi.org/10.1007/978-3-540-70617-5_11
   Google Scholar
• Lal R, Harris D, Postel-Vinay S, et al. Reovirus: rationale and clinical trial update. Curr Opin Mol Ther. 2009;11(5):532–539.
   PubMedGoogle Scholar
• Kirn DH, Thorne SH. Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat Rev Cancer. 2009;9(1):64–71. DOI:https://doi.org/10.1038/nrc2545
   Google Scholar
• Grandi P, Peruzzi P, Reinhart B, et al. Design and application of oncolytic HSV vectors for glioblastoma therapy. Expert Rev Neurother. 2009;9(4):505–517. DOI:https://doi.org/10.1586/ern.09.9
   Google Scholar
• Lorence RM, Roberts MS, O’Neil JD, et al. Phase 1 clinical experience using intravenous administration of PV701, an oncolytic Newcastle disease virus. Curr Cancer Drug Targets. 2007;7(2):157–167. DOI:https://doi.org/10.2174/156800907780058853
   PubMed Web of Science ®Google Scholar
• Yoon TK, Shichinohe T, Laquerre S, et al. Selectively replicating adenoviruses for oncolytic therapy. Curr Cancer Drug Targets. 2001;1(2):85–107. DOI:https://doi.org/10.2174/1568009013334223
   Google Scholar
• Dock G. Influence of complicating diseases upon leukaemia. J Med Sci. 1904;127:563–592.
   Google Scholar
• Sinkovics JG, Horvath JC. Newcastle disease virus (NDV): brief history of its oncolytic strains. J Clin Virol. 2000;16(1):1–15. DOI:https://doi.org/10.1016/S1386-6532(99)00072-4
   Google Scholar
• Russell SJ. Replicating vectors for cancer therapy: a question of strategy. Semin Cancer Biol. 1994;5(6):437–443.
   PubMed Web of Science ®Google Scholar
• Heiber JF, Barber GN. Evaluation of innate immune signaling pathways in transformed cells. Methods Mol Biol. 2012;797:217–238. DOI:https://doi.org/10.1007/978-1-61779-340-0_15
   Google Scholar
• Naik S, Russell SJ. Engineering oncolytic viruses to exploit tumor specific defects in innate immune signaling pathways. Expert Opin Biol Ther. 2009;9(9):1163–1176. DOI:https://doi.org/10.1517/14712590903170653
   Google Scholar
• Arens R. Rational design of vaccines: learning from immune evasion mechanisms of persistent viruses and tumors. Adv Immunol. 2012;114:217–243. DOI:https://doi.org/10.1016/B978-0-12-396548-6.00009-3
   Google Scholar
• Butt AQ, Mills KH. Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines. Oncogene. 2014;33(38):4623–4631. DOI:https://doi.org/10.1038/onc.2013.432
   Google Scholar
• Logg CR, Tai CK, Logg A, et al. A uniquely stable replication-competent retrovirus vector achieves efficient gene delivery in vitro and in solid tumors. Hum Gene Ther. 2001;12(8):921–932. DOI:https://doi.org/10.1089/104303401750195881
   Google Scholar
• Perez OD, Logg CR, Hiraoka K, et al. Design and Selection of Toca 511 for Clinical Use: modified Retroviral Replicating Vector With Improved Stability and Gene Expression. Mol Ther. 2012;20(9):1689-1698. DOI:https://doi.org/10.1038/mt.2012.83
   Google Scholar
• Lin AH, Twitty CG, Burnett R, et al. Retroviral replicating vector delivery of miR-PDL1 Inhibits immune checkpoint PDL1 and enhances immune responses in vitro. Mol Ther Nucleic Acids. 2017;6:221–232. DOI:https://doi.org/10.1016/j.omtn.2016.11.007
   Google Scholar
• Hofacre A, Yagiz K, Mendoza D, et al. Efficient therapeutic protein expression using retroviral replicating vector with 2A peptide in cancer models. Hum Gene Ther. 2018;29(4):437–451. DOI:https://doi.org/10.1089/hum.2017.205
   Google Scholar
• Logg CR, Kasahara N. Retrovirus-mediated gene transfer to tumors: utilizing the replicative power of viruses to achieve highly efficient tumor transduction in vivo. Methods Mol Biol. 2004;246:499–525. DOI:https://doi.org/10.1385/1-59259-650-9:499
   Google Scholar
• Dalba C, Klatzmann D, Logg CR, et al. Beyond oncolytic virotherapy: replication-competent retrovirus vectors for selective and stable transduction of tumors. Curr Gene Ther. 2005;5(6):655–667. DOI:https://doi.org/10.2174/156652305774964659
   Google Scholar
• Tai CK, Kasahara N. Replication-competent retrovirus vectors for cancer gene therapy. Front Biosci. 2008;13:3083–3095. DOI:https://doi.org/10.2741/2910
   Google Scholar
• Logg CR, Robbins JM, Jolly DJ, et al. Retroviral replicating vectors in cancer. Methods Enzymol. 2012;507:199–228. DOI:https://doi.org/10.1016/B978-0-12-386509-0.00011-9
   Google Scholar
• Lin AH, Burrascano C, Pettersson PL, et al. Blockade of type I interferon (IFN) production by retroviral replicating vectors and reduced tumor cell responses to IFN likely contribute to tumor selectivity. J Virol. 2014;88(17):10066–10077. DOI:https://doi.org/10.1128/JVI.02300-13
   Google Scholar
• Sheridan PL, Bodner M, Lynn A, et al. Generation of retroviral packaging and producer cell lines for large-scale vector production and clinical application: improved safety and high titer. Mol Ther. 2000;2(3):262–275. DOI:https://doi.org/10.1006/mthe.2000.0123
   Google Scholar
• Jolly DJ, Ibanez C. Producer Cells for Replication Competent Retroviral Vectors. United States Patent Number:US 10,316,333 B2, Assignee:Tocagen Inc. Granted: June 11, 2019.
   Google Scholar
• Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol. 1994;68(1):510–516. DOI:https://doi.org/10.1128/JVI.68.1.510-516.1994
   Google Scholar
• Hiraoka K, Kimura T, Logg CR, et al. Therapeutic efficacy of replication-competent retrovirus vector-mediated suicide gene therapy in a multifocal colorectal cancer metastasis model. Cancer Res. 2007;67(11):5345–5353. DOI:https://doi.org/10.1158/0008-5472.CAN-06-4673
   Google Scholar
• Kikuchi E, Menendez S, Ozu C, et al. Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts. Cancer Gene Ther. 2007;14(3):279–286.
   PubMed Web of Science ®Google Scholar
• Kubo S, Takagi-Kimura M, Logg CR, et al. Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus. Cancer Gene Ther. 2013;20(12):671–677. DOI:https://doi.org/10.1038/cgt.2013.67
   Google Scholar
• Ostertag D, Amundson KK, Lopez Espinoza F, et al. Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. Neuro Oncol. 2012;14(2):145–159. DOI:https://doi.org/10.1093/neuonc/nor199.
   PubMed Web of Science ®Google Scholar
• Reik W, Weiher H, Jaenisch R. Replication-competent Moloney murine leukemia virus carrying a bacterial suppressor tRNA gene: selective cloning of proviral and flanking host sequences. Proc Natl Acad Sci U S A. 1985;82(4):1141–1145. DOI:https://doi.org/10.1073/pnas.82.4.1141
   Google Scholar
• Tai CK, Wang W, Lai YH, et al. Enhanced efficiency of prodrug activation therapy by tumor-selectively replicating retrovirus vectors armed with the Escherichia coli purine nucleoside phosphorylase gene. Cancer Gene Ther. 2010;17(9):614–623. DOI:https://doi.org/10.1038/cgt.2010.17
   Google Scholar
• Tai CK, Wang WJ, Chen TC, et al. Single-shot, multicycle suicide gene therapy by replication-competent retrovirus vectors achieves long-term survival benefit in experimental glioma. Mol Ther. 2005;12(5):842–851. DOI:https://doi.org/10.1016/j.ymthe.2005.03.017.
   PubMed Web of Science ®Google Scholar
• Cloughesy TF, Landolfi J, Hogan DJ, et al. Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. Sci Transl Med. 2016;8(341):341ra375. DOI:https://doi.org/10.1126/scitranslmed.aad9784.
   Google Scholar
• Cloughesy TF, Landolfi J, Vogelbaum MA, et al. Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Neuro Oncol. 2018;20(10):1383–1392. DOI:https://doi.org/10.1093/neuonc/noy075.
   Google Scholar
• Goff S, Traktman P, Baltimore D. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J Virol. 1981;38(1):239–248. DOI:https://doi.org/10.1128/JVI.38.1.239-248.1981
   Google Scholar
• Stuhlmann H, Jaenisch R, Mulligan RC. Construction and properties of replication-competent murine retroviral vectors encoding methotrexate resistance. Mol Cell Biol. 1989;9(1):100–108. DOI:https://doi.org/10.1128/MCB.9.1.100
   Google Scholar
• Logg CR, Logg A, Matusik RJ, et al. Tissue-specific transcriptional targeting of a replication-competent retroviral vector. J Virol. 2002;76(24):12783–12791. DOI:https://doi.org/10.1128/JVI.76.24.12783-12791.2002
   Google Scholar
• Wang W, Tai CK, Kasahara N, et al. Highly efficient and tumor-restricted gene transfer to malignant gliomas by replication-competent retrovirus vectors. Hum Gene Ther. 2003;14(2):117–127. DOI:https://doi.org/10.1089/104303403321070810
   Google Scholar
• Hiraoka K, Kimura T, Logg CR, et al. Tumor-selective gene expression in a hepatic metastasis model after locoregional delivery of a replication-competent retrovirus vector. Clin Cancer Res. 2006;12(23):7108–7116. DOI:https://doi.org/10.1158/1078-0432.CCR-06-1452
   Google Scholar
• Wang W, Tai CK, Kershaw AD, et al. Use of replication-competent retroviral vectors in an immune competent intracranial glioma model. Neurosurg Focus. 2006;20(4):E25. DOI:https://doi.org/10.3171/foc.2006.20.4.1
   Google Scholar
• Kikuchi E, Menendez S, Ozu C, et al. Highly efficient gene delivery for bladder cancers by intravesically administered replication-competent retroviral vectors. Clin Cancer Res. 2007;13(45115 Pt 1):1–4518. DOI:https://doi.org/10.1158/1078-0432.CCR-07-0151
   Google Scholar
• Kimura T, Hiraoka K, Kasahara N, et al. Optimization of enzyme-substrate pairing for bioluminescence imaging of gene transfer using Renilla and Gaussia luciferases. J Gene Med. 2010;12(6):528–537. DOI:https://doi.org/10.1002/jgm.1463
   Google Scholar
• Yin D, Zhai Y, Gruber HE, et al. Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. Cancer Gene Ther. 2013;20(6):336–341. DOI:https://doi.org/10.1038/cgt.2013.25
   Google Scholar
• Solly SK, Trajcevski S, Frisen C, et al. Replicative retroviral vectors for cancer gene therapy. Cancer Gene Ther. 2003;10(1):30–39. DOI:https://doi.org/10.1038/sj.cgt.7700521
   Google Scholar
• Trajcevski S, Solly SK, Frisen C, et al. Characterization of a semi-replicative gene delivery system allowing propagation of complementary defective retroviral vectors. J Gene Med. 2005;7(3):276–287. DOI:https://doi.org/10.1002/jgm.663
   Google Scholar
• Qiao J, Moreno J, Sanchez-Perez L, et al. VSV-G pseudotyped, MuLV-based, semi-replication-competent retrovirus for cancer treatment. Gene Ther. 2006;13(20):1457–1470. DOI:https://doi.org/10.1038/sj.gt.3302782
   PubMed Web of Science ®Google Scholar
• Duerner LJ, Schwantes A, Schneider IC, et al. Cell entry targeting restricts biodistribution of replication-competent retroviruses to tumour tissue. Gene Ther. 2008;15(22):1500–1510. DOI:https://doi.org/10.1038/gt.2008.92
   Google Scholar
• Hlavaty J, Jandl G, Liszt M, et al. Comparative evaluation of preclinical in vivo models for the assessment of replicating retroviral vectors for the treatment of glioblastoma. J Neurooncol. 2011;102(1):59–69. DOI:https://doi.org/10.1007/s11060-010-0295-5
   Google Scholar
• Inoko K, Hiraoka K, Inagaki A, et al. Therapeutic activity of retroviral replicating vector-mediated prodrug activator gene therapy for pancreatic cancer. Cancer Gene Ther. 2018;25(7-8):184-195. DOI:https://doi.org/10.1038/s41417-018-0020-7
   Google Scholar
• Twitty CG, Diago OR, Hogan DJ, et al. Retroviral replicating vectors deliver cytosine deaminase leading to targeted 5-fluorouracil-mediated cytotoxicity in multiple human cancer types. Hum Gene Ther Methods. 2016;27(1):17–31. DOI:https://doi.org/10.1089/hgtb.2015.106
   Google Scholar
• Tamura K, Tamura M, Ikenaka K, et al. Eradication of murine brain tumors by direct inoculation of concentrated high titer-recombinant retrovirus harboring the herpes simplex virus thymidine kinase gene. Gene Ther. 2001;8(3):215–222. DOI:https://doi.org/10.1038/sj.gt.3301371
   Google Scholar
• Hiraoka K, Inagaki A, Kato Y, et al. Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity. Neuro Oncol. 2017;19(7):918–929. DOI:https://doi.org/10.1093/neuonc/nox038.
   Google Scholar
• Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–338. DOI:https://doi.org/10.1038/nrc1074
   Google Scholar
• Heidelberger, C. Biochemical mechanisms of action of fluorinated pyrimidines. Exp Cell Res. 1963;24(SUPPL9):462–471. DOI:https://doi.org/10.1016/0014-4827(63)90286-6
   Google Scholar
• Sakamoto S, Kasahara N, Iwama T. Thymidine Kinase Activities in Familial Adenomatous Polyposis, Adenomatous Polyps, and Carcinoma of the Colon. in Familial Adenomatous Polyposis. Herrera L, ed. New York: A.R. Liss; 1990. p. 315–324.
   Google Scholar
• Touil Y, Igoudjil W, Corvaisier M, et al. Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis. Clin Cancer Res. 2014;20(4):837–846. DOI:https://doi.org/10.1158/1078-0432.CCR-13-1854
   Google Scholar
• Brown JA, Yonekubo Y, Hanson N, et al. TGF-beta-induced quiescence mediates chemoresistance of tumor-propagating cells in squamous cell carcinoma. Cell Stem Cell. 2017;21(5):650–664.e8. DOI:https://doi.org/10.1016/j.stem.2017.10.001
   Google Scholar
• Mitchell LA, Lopez Espinoza F, Mendoza D, et al. Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model. Neuro Oncol. 2017;19(7):930–939. DOI:https://doi.org/10.1093/neuonc/nox037.
   PubMed Web of Science ®Google Scholar
• Yagiz K, Rodriguez-Aguirre ME, Lopez Espinoza F, et al. A Retroviral replicating vector encoding cytosine deaminase and 5-FC induces immune memory in metastatic colorectal cancer models. Mol Ther Oncolytics. 2017;8:14–26. DOI:https://doi.org/10.1016/j.omto.2017.12.001
   Google Scholar
• Gmeiner WH. Fluoropyrimidine modulation of the anti-tumor immune response-prospects for improved colorectal cancer treatment. Cancers (Basel). 2020;12(6):1641. DOI:https://doi.org/10.3390/cancers12061641
   Google Scholar
• Mathews CK. Deoxyribonucleotide metabolism, mutagenesis and cancer. Nat Rev Cancer. 2015;15(9):528–539. DOI:https://doi.org/10.1038/nrc3981
   PubMed Web of Science ®Google Scholar
• Takahashi M, Valdes G, Hiraoka K, et al. Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector. Cancer Gene Ther. 2014;21(10):405–410. DOI:https://doi.org/10.1038/cgt.2014.38
   Google Scholar
• Huang TT, Parab S, Burnett R, et al. Intravenous administration of retroviral replicating vector, Toca 511, demonstrates therapeutic efficacy in orthotopic immune-competent mouse glioma model. Hum Gene Ther. 2015;26(2):82–93. DOI:https://doi.org/10.1089/hum.2014.100.
   PubMed Web of Science ®Google Scholar
• Kubo S, Takagi-Kimura M, Tagawa M, et al. Dual-vector prodrug activator gene therapy using retroviral replicating vectors. Cancer Gene Ther. 2019;26(5-6):128–135. DOI:https://doi.org/10.1038/s41417-018-0051-0
   Google Scholar
• Chen SH, Sun JM, Chen BM, et al. Efficient prodrug activator gene therapy by retroviral replicating vectors prolongs survival in an immune-competent intracerebral glioma model. Int J Mol Sci. 2020;21(4):1433. DOI:https://doi.org/10.3390/ijms21041433
   Google Scholar
• Collins SA, Kamath P, Matsuura S, et al. Therapeutic efficacy of vocimagene amiretrorepvec (Toca 511) prodrug activator gene therapy in peritoneal carcinomatosis models of ovarian cancer. Gynecol Oncol. 2019;154(1):E29–E30. DOI:https://doi.org/10.1016/j.ygyno.2019.03.231.
   PubMed Web of Science ®Google Scholar
• Stupp R, Mason WP, Van Den Bent MJ, et al., European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–996. DOI:https://doi.org/10.1056/NEJMoa043330.
   PubMed Web of Science ®Google Scholar
• Gorlia T, Stupp R, Brandes AA, et al. New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer. 2012;48(8):1176–1184. DOI:https://doi.org/10.1016/j.ejca.2012.02.004
   Google Scholar
• Stupp R, Hegi ME, Mason WP, et al., European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–466. DOI:https://doi.org/10.1016/S1470-2045(09)70025-7.
   PubMed Web of Science ®Google Scholar
• Aghi M, Vogelbaum MA, Jolly DJ, et al. ST-001 Phase 1 Trial of a retroviral replicating vector (Toca 511) in recurrent high grade glioma patients demonstrates the importance of real-time MRI-guided delivery for dose-related evaluation of safety and efficacy. Neuro Oncol. 2013;15(suppl 3):iii217–iii225. DOI:https://doi.org/10.1093/neuonc/not191
   Google Scholar
• Aghi M, Vogelbaum MA, Kesari S, et al. AT-02 Intratumoral delivery of the retroviral replicating vector (RRV) Toca 511 in subjects with recurrent high grade glioma: interim report of a Phase I study (NCT 01156584). Neuro Oncol. 2014;16(suppl 5):v8. DOI:https://doi.org/10.1093/neuonc/nou237.2.
   Web of Science ®Google Scholar
• Clarke JL, Ennis MM, Yung WKA, et al., North American Brain Tumor Consortium. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? Neuro Oncol. 2011;13(10):1118–1124. DOI:https://doi.org/10.1093/neuonc/nor110.
   Web of Science ®Google Scholar
• Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010;28(7):1168–1174. DOI:https://doi.org/10.1200/JCO.2009.23.2595.
   PubMed Web of Science ®Google Scholar
• Accomando WP, Rao AR, Hogan DJ, et al. Molecular and immunologic signatures are related to clinical benefit from treatment with vocimagene amiretrorepvec (Toca 511) and 5-fluorocytosine (Toca FC) in patients with glioma. Clin Cancer Res. 2020;26(23):6176–6186. DOI:https://doi.org/10.1158/1078-0432.CCR-20-0536.
   Web of Science ®Google Scholar
• Walbert T, Bota D, Vogelbaum M, et al. ATIM-21. Intravenous delivery of Toca 511 in patients with high grade glioma results in quantifiable expression of cytosine deaminase in tumor tissue. Neuro Oncol. 2017;19(suppl_6):vi30–vi31. DOI:https://doi.org/10.1093/neuonc/nox168.116.
   Google Scholar
• Cloughesy T, Walbert T, Bota D, et al. ATIM-02. Successful cancer-selective gene delivery following intravenous Toca 511 delivery in patients with recurrent high grade glioma (HGG). Neuro Oncol. 2016;18(suppl_6):vi17. DOI:https://doi.org/10.1093/neuonc/now212.067
   Google Scholar
• Kalkanis S, Jolly DJ, Pertschuk D, et al. AT-29. Intravenous administration of Toca 511 in patients with recurrent glioblastoma. Neuro Oncol. 2014;16(suppl 5):v15. DOI:https://doi.org/10.1093/neuonc/nou237.29.
   Web of Science ®Google Scholar
• Hogan DJ, Zhu JJ, Diago OR, et al. Molecular analyses support the safety and activity of retroviral replicating vector Toca 511 in patients. Clin Cancer Res. 2018;24(19):4680–4693. DOI:https://doi.org/10.1158/1078-0432.CCR-18-0619
   Google Scholar
• Cloughesy TF, Petrecca K, Walbert T, et al. Effect of vocimagene amiretrorepvec in combination with flucytosine vs standard of care on survival following tumor resection in patients with recurrent high-grade glioma: a randomized clinical trial. JAMA Oncol. 2020;6(12):1939–1946. DOI:https://doi.org/10.1001/jamaoncol.2020.3161.
   Google Scholar
• Cloughesy TF, Petrecca K, Walbert T, et al. LTBK-08. Toca 511 & Toca FC versus standard of care in patients with recurrent high grade glioma. Neuro Oncol. 2019;21(Suppl_6):vi284. DOI:https://doi.org/10.1093/neuonc/noz219.1199.
   Google Scholar
• Falchook GS, Rodon Ahnert J, Venkat S, et al. Immune modulation after Toca 511 and Toca FC treatment of colorectal cancer patients. J Clin Oncol. 2020;38(4_suppl):186. DOI:https://doi.org/10.1200/JCO.2020.38.4_suppl.186
   Google Scholar
• Ahluwalia M, Pugh S, Ellingson B, et al. RBTT-11. NRG Oncology NRG-BN006: a Phase II/III randomized, open-label study of Toca 511 and Toca FC with standard of care compared to standard of care in patients with newly diagnosed glioblastoma. Neuro Oncol. 2019;21(Suppl_6):vi220–vi221. DOI:https://doi.org/10.1093/neuonc/noz175.922.
   Google Scholar
• Cornetta K, Morgan RA, Gillio A, et al. No retroviremia or pathology in long-term follow-up of monkeys exposed to a murine amphotropic retrovirus. Hum Gene Ther. 1991;2(3):215–219. DOI:https://doi.org/10.1089/hum.1991.2.3-215
   Google Scholar
• Huang TT, Hlavaty J, Ostertag D, et al. Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive glioblastoma model. Cancer Gene Ther. 2013;20(10):544–551. DOI:https://doi.org/10.1038/cgt.2013.51
   Google Scholar
• Mitchell LA, Yagiz K, Hofacre A, et al. PD-L1 checkpoint blockade delivered by retroviral replicating vector confers anti-tumor efficacy in murine tumor models. Oncotarget. 2019;10(23):2252–2269. DOI:https://doi.org/10.18632/oncotarget.26785
   Google Scholar
• Zupanc GKH, Zupanc FB, Sipahi R. Stochastic cellular automata model of tumorous neurosphere growth: roles of developmental maturity and cell death. J Theor Biol. 2019;467:100–110. DOI:https://doi.org/10.1016/j.jtbi.2019.01.028
   Google Scholar
• Simnica D, Akyuz N, Schliffke S, et al. T cell receptor next-generation sequencing reveals cancer-associated repertoire metrics and reconstitution after chemotherapy in patients with hematological and solid tumors. Oncoimmunology. 2019;8(11):e1644110. DOI:https://doi.org/10.1080/2162402X.2019.1644110.
   PubMed Web of Science ®Google Scholar