Preclinical Pharmacology and Toxicology of Intravenous MV‐NIS, an Oncolytic Measles Virus Administered With or Without Cyclophosphamide
MV‐NIS is an oncolytic measles virus encoding the human thyroidal sodium iodide symporter (NIS). Here, we report the results of preclinical pharmacology and toxicology studies conducted in support of our clinical protocol “Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2007-12, Vol.82 (6), p.700-710 |
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| creator | Myers, R M Greiner, S M Harvey, M E Griesmann, G Kuffel, M J Buhrow, S A Reid, J M Federspiel, M Ames, M M Dingli, D Schweikart, K Welch, A Dispenzieri, A Peng, K‐W Russell, S J |
| description | MV‐NIS is an oncolytic measles virus encoding the human thyroidal sodium iodide symporter (NIS). Here, we report the results of preclinical pharmacology and toxicology studies conducted in support of our clinical protocol “Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, with or without Cyclophosphamide, in Patients with Recurrent or Refractory Multiple Myeloma.” Dose–response studies in the KAS‐6/1 myeloma xenograft model demonstrated a minimum effective dose of 4 × 106 TCID50 (tissue culture infectious dose 50)/kg. Toxicity studies in measles‐naive squirrel monkeys and measles‐susceptible transgenic mice were negative at intravenous doses up to 108 and 4 × 108 TCID50/kg, respectively. Abundant viral mRNA, maximal on day 8, was detected in cheek swabs of squirrel monkeys, more so after pretreatment with cyclophosphamide. On the basis of these data, the safe starting dose of MV‐NIS for our clinical protocol was set at 1−2 × 104 TCID50/kg (106 TCID50 per patient).
Clinical Pharmacology & Therapeutics (2007) 82, 700–710; doi:10.1038/sj.clpt.6100409; published online 31 October 2007 |
| doi_str_mv | 10.1038/sj.clpt.6100409 |
| format | Article |
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Clinical Pharmacology & Therapeutics (2007) 82, 700–710; doi:10.1038/sj.clpt.6100409; published online 31 October 2007</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1038/sj.clpt.6100409</identifier><identifier>PMID: 17971816</identifier><identifier>CODEN: CLPTAT</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents, Alkylating - pharmacology ; Biological and medical sciences ; Cell Line, Tumor ; Cyclophosphamide - administration & dosage ; Cyclophosphamide - pharmacology ; Female ; Humans ; Injections, Intravenous ; Measles virus - genetics ; Measles virus - isolation & purification ; Medical sciences ; Membrane Cofactor Protein - genetics ; Mice ; Mice, Inbred ICR ; Mice, SCID ; Mice, Transgenic ; Multiple Myeloma - drug therapy ; Oncolytic Virotherapy - adverse effects ; Oncolytic Virotherapy - methods ; Oncolytic Viruses ; Pharmacology. Drug treatments ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Viral - isolation & purification ; Saimiri ; Symporters - administration & dosage ; Symporters - pharmacology ; Transplantation, Heterologous</subject><ispartof>Clinical pharmacology and therapeutics, 2007-12, Vol.82 (6), p.700-710</ispartof><rights>2007 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4699-7cb303957c6a0b2951fb142bcd66fcc5f21dda4c251a90ca327421cfc47943973</citedby><cites>FETCH-LOGICAL-c4699-7cb303957c6a0b2951fb142bcd66fcc5f21dda4c251a90ca327421cfc47943973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Fsj.clpt.6100409$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Fsj.clpt.6100409$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19886615$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17971816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Myers, R M</creatorcontrib><creatorcontrib>Greiner, S M</creatorcontrib><creatorcontrib>Harvey, M E</creatorcontrib><creatorcontrib>Griesmann, G</creatorcontrib><creatorcontrib>Kuffel, M J</creatorcontrib><creatorcontrib>Buhrow, S A</creatorcontrib><creatorcontrib>Reid, J M</creatorcontrib><creatorcontrib>Federspiel, M</creatorcontrib><creatorcontrib>Ames, M M</creatorcontrib><creatorcontrib>Dingli, D</creatorcontrib><creatorcontrib>Schweikart, K</creatorcontrib><creatorcontrib>Welch, A</creatorcontrib><creatorcontrib>Dispenzieri, A</creatorcontrib><creatorcontrib>Peng, K‐W</creatorcontrib><creatorcontrib>Russell, S J</creatorcontrib><title>Preclinical Pharmacology and Toxicology of Intravenous MV‐NIS, an Oncolytic Measles Virus Administered With or Without Cyclophosphamide</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>MV‐NIS is an oncolytic measles virus encoding the human thyroidal sodium iodide symporter (NIS). Here, we report the results of preclinical pharmacology and toxicology studies conducted in support of our clinical protocol “Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, with or without Cyclophosphamide, in Patients with Recurrent or Refractory Multiple Myeloma.” Dose–response studies in the KAS‐6/1 myeloma xenograft model demonstrated a minimum effective dose of 4 × 106 TCID50 (tissue culture infectious dose 50)/kg. Toxicity studies in measles‐naive squirrel monkeys and measles‐susceptible transgenic mice were negative at intravenous doses up to 108 and 4 × 108 TCID50/kg, respectively. Abundant viral mRNA, maximal on day 8, was detected in cheek swabs of squirrel monkeys, more so after pretreatment with cyclophosphamide. On the basis of these data, the safe starting dose of MV‐NIS for our clinical protocol was set at 1−2 × 104 TCID50/kg (106 TCID50 per patient).
Clinical Pharmacology & Therapeutics (2007) 82, 700–710; doi:10.1038/sj.clpt.6100409; published online 31 October 2007</description><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents, Alkylating - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Cyclophosphamide - pharmacology</subject><subject>Female</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Measles virus - genetics</subject><subject>Measles virus - isolation & purification</subject><subject>Medical sciences</subject><subject>Membrane Cofactor Protein - genetics</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Mice, SCID</subject><subject>Mice, Transgenic</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Oncolytic Virotherapy - adverse effects</subject><subject>Oncolytic Virotherapy - methods</subject><subject>Oncolytic Viruses</subject><subject>Pharmacology. Drug treatments</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Viral - isolation & purification</subject><subject>Saimiri</subject><subject>Symporters - administration & dosage</subject><subject>Symporters - pharmacology</subject><subject>Transplantation, Heterologous</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv0zAUxy0EYl3hzA35wo10tpM49QVpqsaotLFKlHG0nBdnceXEkZ0OcuPKjc_IJ8GlgcGJ09OTf-__nvVD6AUlC0rS5VnYLcD2w4JTQjIiHqEZzVOW8DzNH6MZIUQkgqX8BJ2GsIttJpbLp-iEFqKgS8pn6NvGa7CmM6As3jTKtwqcdXcjVl2Ft-6LmVpX43U3eHWvO7cP-Pr2x9fv79cfXkcO33QRGgcD-FqrYHXAt8ZH6LxqY3IYtNcV_mSGBjv_q7r9gFcjWNc3LvSNak2ln6EntbJBP5_qHH18e7FdvUuubi7Xq_OrBDIuRFJAmZJU5AVwRUomclqXNGMlVJzXAHnNaFWpDFhOlSCgUlZkjEINWSGyVBTpHL055vb7stUV6MOvrOy9aZUfpVNG_vvSmUbeuXvJCi5yzmPA2TEAvAvB6_rPLCXyYEWGnTxYkZOVOPHy75UP_KQhAq8mQIUoovaqAxMeuGiN82h2jooj99lYPf5vr1xttr9P-Amxma0J</recordid><startdate>200712</startdate><enddate>200712</enddate><creator>Myers, R M</creator><creator>Greiner, S M</creator><creator>Harvey, M E</creator><creator>Griesmann, G</creator><creator>Kuffel, M J</creator><creator>Buhrow, S A</creator><creator>Reid, J M</creator><creator>Federspiel, M</creator><creator>Ames, M M</creator><creator>Dingli, D</creator><creator>Schweikart, K</creator><creator>Welch, A</creator><creator>Dispenzieri, A</creator><creator>Peng, K‐W</creator><creator>Russell, S J</creator><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>200712</creationdate><title>Preclinical Pharmacology and Toxicology of Intravenous MV‐NIS, an Oncolytic Measles Virus Administered With or Without Cyclophosphamide</title><author>Myers, R M ; Greiner, S M ; Harvey, M E ; Griesmann, G ; Kuffel, M J ; Buhrow, S A ; Reid, J M ; Federspiel, M ; Ames, M M ; Dingli, D ; Schweikart, K ; Welch, A ; Dispenzieri, A ; Peng, K‐W ; Russell, S J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4699-7cb303957c6a0b2951fb142bcd66fcc5f21dda4c251a90ca327421cfc47943973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents, Alkylating - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Cyclophosphamide - pharmacology</topic><topic>Female</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Measles virus - genetics</topic><topic>Measles virus - isolation & purification</topic><topic>Medical sciences</topic><topic>Membrane Cofactor Protein - genetics</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Mice, SCID</topic><topic>Mice, Transgenic</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Oncolytic Virotherapy - adverse effects</topic><topic>Oncolytic Virotherapy - methods</topic><topic>Oncolytic Viruses</topic><topic>Pharmacology. Drug treatments</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Viral - isolation & purification</topic><topic>Saimiri</topic><topic>Symporters - administration & dosage</topic><topic>Symporters - pharmacology</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Myers, R M</creatorcontrib><creatorcontrib>Greiner, S M</creatorcontrib><creatorcontrib>Harvey, M E</creatorcontrib><creatorcontrib>Griesmann, G</creatorcontrib><creatorcontrib>Kuffel, M J</creatorcontrib><creatorcontrib>Buhrow, S A</creatorcontrib><creatorcontrib>Reid, J M</creatorcontrib><creatorcontrib>Federspiel, M</creatorcontrib><creatorcontrib>Ames, M M</creatorcontrib><creatorcontrib>Dingli, D</creatorcontrib><creatorcontrib>Schweikart, K</creatorcontrib><creatorcontrib>Welch, A</creatorcontrib><creatorcontrib>Dispenzieri, A</creatorcontrib><creatorcontrib>Peng, K‐W</creatorcontrib><creatorcontrib>Russell, S J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Myers, R M</au><au>Greiner, S M</au><au>Harvey, M E</au><au>Griesmann, G</au><au>Kuffel, M J</au><au>Buhrow, S A</au><au>Reid, J M</au><au>Federspiel, M</au><au>Ames, M M</au><au>Dingli, D</au><au>Schweikart, K</au><au>Welch, A</au><au>Dispenzieri, A</au><au>Peng, K‐W</au><au>Russell, S J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical Pharmacology and Toxicology of Intravenous MV‐NIS, an Oncolytic Measles Virus Administered With or Without Cyclophosphamide</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2007-12</date><risdate>2007</risdate><volume>82</volume><issue>6</issue><spage>700</spage><epage>710</epage><pages>700-710</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><coden>CLPTAT</coden><abstract>MV‐NIS is an oncolytic measles virus encoding the human thyroidal sodium iodide symporter (NIS). Here, we report the results of preclinical pharmacology and toxicology studies conducted in support of our clinical protocol “Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, with or without Cyclophosphamide, in Patients with Recurrent or Refractory Multiple Myeloma.” Dose–response studies in the KAS‐6/1 myeloma xenograft model demonstrated a minimum effective dose of 4 × 106 TCID50 (tissue culture infectious dose 50)/kg. Toxicity studies in measles‐naive squirrel monkeys and measles‐susceptible transgenic mice were negative at intravenous doses up to 108 and 4 × 108 TCID50/kg, respectively. Abundant viral mRNA, maximal on day 8, was detected in cheek swabs of squirrel monkeys, more so after pretreatment with cyclophosphamide. On the basis of these data, the safe starting dose of MV‐NIS for our clinical protocol was set at 1−2 × 104 TCID50/kg (106 TCID50 per patient).
Clinical Pharmacology & Therapeutics (2007) 82, 700–710; doi:10.1038/sj.clpt.6100409; published online 31 October 2007</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>17971816</pmid><doi>10.1038/sj.clpt.6100409</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical pharmacology and therapeutics, 2007-12, Vol.82 (6), p.700-710 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacology Antineoplastic Agents, Alkylating - pharmacology Biological and medical sciences Cell Line, Tumor Cyclophosphamide - administration & dosage Cyclophosphamide - pharmacology Female Humans Injections, Intravenous Measles virus - genetics Measles virus - isolation & purification Medical sciences Membrane Cofactor Protein - genetics Mice Mice, Inbred ICR Mice, SCID Mice, Transgenic Multiple Myeloma - drug therapy Oncolytic Virotherapy - adverse effects Oncolytic Virotherapy - methods Oncolytic Viruses Pharmacology. Drug treatments Reverse Transcriptase Polymerase Chain Reaction RNA, Viral - isolation & purification Saimiri Symporters - administration & dosage Symporters - pharmacology Transplantation, Heterologous |
| title | Preclinical Pharmacology and Toxicology of Intravenous MV‐NIS, an Oncolytic Measles Virus Administered With or Without Cyclophosphamide |
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