A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer
Purpose: Ultra low doses of interleukin-2 (IL-2) can activate the high-affinity IL-2 receptor constitutively expressed on CD56 bright natural killer (NK) cells, the CD34 + NK cell precursor, and CD4 + CD25 + regulatory T cells (Tregs) in vivo . We have previously shown synergy between IL-2 and stem...
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| Veröffentlicht in: | Clinical cancer research 2006-07, Vol.12 (13), p.3993-3996 |
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| container_title | Clinical cancer research |
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| creator | Shah, Manisha H Freud, Aharon G Benson, Jr, Don M Ferkitich, Amy K Dezube, Bruce J Bernstein, Zale P Caligiuri, Michael A |
| description | Purpose: Ultra low doses of interleukin-2 (IL-2) can activate the high-affinity IL-2 receptor constitutively expressed on CD56 bright natural killer (NK) cells, the CD34 + NK cell precursor, and CD4 + CD25 + regulatory T cells (Tregs) in vivo . We have previously shown synergy between IL-2 and stem cell factor (SCF) in the generation of CD56 bright NK cells from CD34 + hemopoietic progenitor cells in vitro and showed synergistic NK cell expansion in an in vivo preclinical model. To determine the safety, toxicity, and immune modulation of this combination of cytokines in vivo , we conducted a first-in-man phase I study.
Experimental Design: A phase I dose escalation study was conducted using IL-2 at 900,000 or 650,000 IU/m 2 /d for 8 weeks with 5 or 10 μg/kg/d of SCF given thrice a week for 8 weeks in patients with HIV infection and/or cancer.
Results: Ten of 13 patients completed therapy; four experienced the dose-limiting toxicities of grade 3 fatigue or urticaria. The
maximum tolerated doses of IL-2 and SCF in combination is 650,000 IU/m 2 /d of IL-2 and 5 μg/kg/d thrice a week of SCF. NK cells were expanded over 2-fold on therapy; Tregs were expanded nearly 6-fold
from baseline.
Conclusions: Administration of IL-2 with SCF is safe and well tolerated and leads to expansion of lymphocyte subsets in patients with
HIV or HIV and cancer; however, the changes in NK cell and Treg expansion seen with this cytokine combination were no different
than those seen with a similar dose of IL-2 alone. |
| doi_str_mv | 10.1158/1078-0432.CCR-06-0268 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17254643</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17254643</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-4878e8f627d7b427be56eda34f323bbc8e08b5aa143ca29dd13771397b09ad353</originalsourceid><addsrcrecordid>eNpFkE1v1DAQhi0EoqXlJ4B8Quohxd92jlWgdKWVqID2ajnOhBiySbEdrfrv63QX9eSR53lnRg9CHyi5pFSaz5RoUxHB2WXT_KiIqghT5hU6pVLqijMlX5f6P3OC3qX0hxAqKBFv0QlVhhpV61O0XOHbwSXAG_wzL90jnnt8N-bo8Hbe4y_z2pkyxBGWv2GqGHZTV0jY4QbGEV87n-eIw4RvXQ4w5YT3IQ_4ZnNfcj34HOYJF2L9WKONmzzEc_Smd2OC98f3DN1df_3V3FTb7982zdW28lyzXAmjDZheMd3pVjDdglTQOS56znjbegPEtNI5Krh3rO46yrWmvNYtqV3HJT9Dnw5zH-L8b4GU7S4kXw53E8xLslQzKZTgBZQH0Mc5pQi9fYhh5-KjpcSuvu3q0q4ubfFtibKr75L7eFywtDvoXlJHwQW4OABD-D3sQwTrnw1ESOCiHyxllnLL65rzJ3mjiAc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17254643</pqid></control><display><type>article</type><title>A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Shah, Manisha H ; Freud, Aharon G ; Benson, Jr, Don M ; Ferkitich, Amy K ; Dezube, Bruce J ; Bernstein, Zale P ; Caligiuri, Michael A</creator><creatorcontrib>Shah, Manisha H ; Freud, Aharon G ; Benson, Jr, Don M ; Ferkitich, Amy K ; Dezube, Bruce J ; Bernstein, Zale P ; Caligiuri, Michael A</creatorcontrib><description>Purpose: Ultra low doses of interleukin-2 (IL-2) can activate the high-affinity IL-2 receptor constitutively expressed on CD56 bright natural killer (NK) cells, the CD34 + NK cell precursor, and CD4 + CD25 + regulatory T cells (Tregs) in vivo . We have previously shown synergy between IL-2 and stem cell factor (SCF) in the generation of CD56 bright NK cells from CD34 + hemopoietic progenitor cells in vitro and showed synergistic NK cell expansion in an in vivo preclinical model. To determine the safety, toxicity, and immune modulation of this combination of cytokines in vivo , we conducted a first-in-man phase I study.
Experimental Design: A phase I dose escalation study was conducted using IL-2 at 900,000 or 650,000 IU/m 2 /d for 8 weeks with 5 or 10 μg/kg/d of SCF given thrice a week for 8 weeks in patients with HIV infection and/or cancer.
Results: Ten of 13 patients completed therapy; four experienced the dose-limiting toxicities of grade 3 fatigue or urticaria. The
maximum tolerated doses of IL-2 and SCF in combination is 650,000 IU/m 2 /d of IL-2 and 5 μg/kg/d thrice a week of SCF. NK cells were expanded over 2-fold on therapy; Tregs were expanded nearly 6-fold
from baseline.
Conclusions: Administration of IL-2 with SCF is safe and well tolerated and leads to expansion of lymphocyte subsets in patients with
HIV or HIV and cancer; however, the changes in NK cell and Treg expansion seen with this cytokine combination were no different
than those seen with a similar dose of IL-2 alone.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-06-0268</identifier><identifier>PMID: 16818697</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Adult ; CD56 Antigen - immunology ; Clinical Immunology/Biological Therapy ; Clinical Trials ; Cohort Studies ; Colonic Neoplasms - drug therapy ; Cytokines ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug-Related Side Effects and Adverse Reactions ; HIV - drug effects ; HIV Infections - complications ; HIV Infections - drug therapy ; Human immunodeficiency virus ; Humans ; Infusions, Intravenous ; Interleukin-2 - administration & dosage ; Interleukin-2 - adverse effects ; Interleukin-2 - pharmacology ; Killer Cells, Natural - drug effects ; Killer Cells, Natural - immunology ; Lymphoma, Non-Hodgkin - drug therapy ; Maximum Tolerated Dose ; Middle Aged ; Remission Induction ; Stem Cell Factor - administration & dosage ; Stem Cell Factor - adverse effects ; Stem Cell Factor - pharmacology ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Treatment Outcome</subject><ispartof>Clinical cancer research, 2006-07, Vol.12 (13), p.3993-3996</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-4878e8f627d7b427be56eda34f323bbc8e08b5aa143ca29dd13771397b09ad353</citedby><cites>FETCH-LOGICAL-c372t-4878e8f627d7b427be56eda34f323bbc8e08b5aa143ca29dd13771397b09ad353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16818697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shah, Manisha H</creatorcontrib><creatorcontrib>Freud, Aharon G</creatorcontrib><creatorcontrib>Benson, Jr, Don M</creatorcontrib><creatorcontrib>Ferkitich, Amy K</creatorcontrib><creatorcontrib>Dezube, Bruce J</creatorcontrib><creatorcontrib>Bernstein, Zale P</creatorcontrib><creatorcontrib>Caligiuri, Michael A</creatorcontrib><title>A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Ultra low doses of interleukin-2 (IL-2) can activate the high-affinity IL-2 receptor constitutively expressed on CD56 bright natural killer (NK) cells, the CD34 + NK cell precursor, and CD4 + CD25 + regulatory T cells (Tregs) in vivo . We have previously shown synergy between IL-2 and stem cell factor (SCF) in the generation of CD56 bright NK cells from CD34 + hemopoietic progenitor cells in vitro and showed synergistic NK cell expansion in an in vivo preclinical model. To determine the safety, toxicity, and immune modulation of this combination of cytokines in vivo , we conducted a first-in-man phase I study.
Experimental Design: A phase I dose escalation study was conducted using IL-2 at 900,000 or 650,000 IU/m 2 /d for 8 weeks with 5 or 10 μg/kg/d of SCF given thrice a week for 8 weeks in patients with HIV infection and/or cancer.
Results: Ten of 13 patients completed therapy; four experienced the dose-limiting toxicities of grade 3 fatigue or urticaria. The
maximum tolerated doses of IL-2 and SCF in combination is 650,000 IU/m 2 /d of IL-2 and 5 μg/kg/d thrice a week of SCF. NK cells were expanded over 2-fold on therapy; Tregs were expanded nearly 6-fold
from baseline.
Conclusions: Administration of IL-2 with SCF is safe and well tolerated and leads to expansion of lymphocyte subsets in patients with
HIV or HIV and cancer; however, the changes in NK cell and Treg expansion seen with this cytokine combination were no different
than those seen with a similar dose of IL-2 alone.</description><subject>Adult</subject><subject>CD56 Antigen - immunology</subject><subject>Clinical Immunology/Biological Therapy</subject><subject>Clinical Trials</subject><subject>Cohort Studies</subject><subject>Colonic Neoplasms - drug therapy</subject><subject>Cytokines</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Drug-Related Side Effects and Adverse Reactions</subject><subject>HIV - drug effects</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Interleukin-2 - administration & dosage</subject><subject>Interleukin-2 - adverse effects</subject><subject>Interleukin-2 - pharmacology</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphoma, Non-Hodgkin - drug therapy</subject><subject>Maximum Tolerated Dose</subject><subject>Middle Aged</subject><subject>Remission Induction</subject><subject>Stem Cell Factor - administration & dosage</subject><subject>Stem Cell Factor - adverse effects</subject><subject>Stem Cell Factor - pharmacology</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Treatment Outcome</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1v1DAQhi0EoqXlJ4B8Quohxd92jlWgdKWVqID2ajnOhBiySbEdrfrv63QX9eSR53lnRg9CHyi5pFSaz5RoUxHB2WXT_KiIqghT5hU6pVLqijMlX5f6P3OC3qX0hxAqKBFv0QlVhhpV61O0XOHbwSXAG_wzL90jnnt8N-bo8Hbe4y_z2pkyxBGWv2GqGHZTV0jY4QbGEV87n-eIw4RvXQ4w5YT3IQ_4ZnNfcj34HOYJF2L9WKONmzzEc_Smd2OC98f3DN1df_3V3FTb7982zdW28lyzXAmjDZheMd3pVjDdglTQOS56znjbegPEtNI5Krh3rO46yrWmvNYtqV3HJT9Dnw5zH-L8b4GU7S4kXw53E8xLslQzKZTgBZQH0Mc5pQi9fYhh5-KjpcSuvu3q0q4ubfFtibKr75L7eFywtDvoXlJHwQW4OABD-D3sQwTrnw1ESOCiHyxllnLL65rzJ3mjiAc</recordid><startdate>20060701</startdate><enddate>20060701</enddate><creator>Shah, Manisha H</creator><creator>Freud, Aharon G</creator><creator>Benson, Jr, Don M</creator><creator>Ferkitich, Amy K</creator><creator>Dezube, Bruce J</creator><creator>Bernstein, Zale P</creator><creator>Caligiuri, Michael A</creator><general>American Association for Cancer Research</general><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>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20060701</creationdate><title>A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer</title><author>Shah, Manisha H ; Freud, Aharon G ; Benson, Jr, Don M ; Ferkitich, Amy K ; Dezube, Bruce J ; Bernstein, Zale P ; Caligiuri, Michael A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-4878e8f627d7b427be56eda34f323bbc8e08b5aa143ca29dd13771397b09ad353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>CD56 Antigen - immunology</topic><topic>Clinical Immunology/Biological Therapy</topic><topic>Clinical Trials</topic><topic>Cohort Studies</topic><topic>Colonic Neoplasms - drug therapy</topic><topic>Cytokines</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>Drug-Related Side Effects and Adverse Reactions</topic><topic>HIV - drug effects</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Interleukin-2 - administration & dosage</topic><topic>Interleukin-2 - adverse effects</topic><topic>Interleukin-2 - pharmacology</topic><topic>Killer Cells, Natural - drug effects</topic><topic>Killer Cells, Natural - immunology</topic><topic>Lymphoma, Non-Hodgkin - drug therapy</topic><topic>Maximum Tolerated Dose</topic><topic>Middle Aged</topic><topic>Remission Induction</topic><topic>Stem Cell Factor - administration & dosage</topic><topic>Stem Cell Factor - adverse effects</topic><topic>Stem Cell Factor - pharmacology</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shah, Manisha H</creatorcontrib><creatorcontrib>Freud, Aharon G</creatorcontrib><creatorcontrib>Benson, Jr, Don M</creatorcontrib><creatorcontrib>Ferkitich, Amy K</creatorcontrib><creatorcontrib>Dezube, Bruce J</creatorcontrib><creatorcontrib>Bernstein, Zale P</creatorcontrib><creatorcontrib>Caligiuri, Michael A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shah, Manisha H</au><au>Freud, Aharon G</au><au>Benson, Jr, Don M</au><au>Ferkitich, Amy K</au><au>Dezube, Bruce J</au><au>Bernstein, Zale P</au><au>Caligiuri, Michael A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-07-01</date><risdate>2006</risdate><volume>12</volume><issue>13</issue><spage>3993</spage><epage>3996</epage><pages>3993-3996</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Ultra low doses of interleukin-2 (IL-2) can activate the high-affinity IL-2 receptor constitutively expressed on CD56 bright natural killer (NK) cells, the CD34 + NK cell precursor, and CD4 + CD25 + regulatory T cells (Tregs) in vivo . We have previously shown synergy between IL-2 and stem cell factor (SCF) in the generation of CD56 bright NK cells from CD34 + hemopoietic progenitor cells in vitro and showed synergistic NK cell expansion in an in vivo preclinical model. To determine the safety, toxicity, and immune modulation of this combination of cytokines in vivo , we conducted a first-in-man phase I study.
Experimental Design: A phase I dose escalation study was conducted using IL-2 at 900,000 or 650,000 IU/m 2 /d for 8 weeks with 5 or 10 μg/kg/d of SCF given thrice a week for 8 weeks in patients with HIV infection and/or cancer.
Results: Ten of 13 patients completed therapy; four experienced the dose-limiting toxicities of grade 3 fatigue or urticaria. The
maximum tolerated doses of IL-2 and SCF in combination is 650,000 IU/m 2 /d of IL-2 and 5 μg/kg/d thrice a week of SCF. NK cells were expanded over 2-fold on therapy; Tregs were expanded nearly 6-fold
from baseline.
Conclusions: Administration of IL-2 with SCF is safe and well tolerated and leads to expansion of lymphocyte subsets in patients with
HIV or HIV and cancer; however, the changes in NK cell and Treg expansion seen with this cytokine combination were no different
than those seen with a similar dose of IL-2 alone.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>16818697</pmid><doi>10.1158/1078-0432.CCR-06-0268</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Clinical cancer research, 2006-07, Vol.12 (13), p.3993-3996 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult CD56 Antigen - immunology Clinical Immunology/Biological Therapy Clinical Trials Cohort Studies Colonic Neoplasms - drug therapy Cytokines Dose-Response Relationship, Drug Drug Administration Schedule Drug-Related Side Effects and Adverse Reactions HIV - drug effects HIV Infections - complications HIV Infections - drug therapy Human immunodeficiency virus Humans Infusions, Intravenous Interleukin-2 - administration & dosage Interleukin-2 - adverse effects Interleukin-2 - pharmacology Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Lymphoma, Non-Hodgkin - drug therapy Maximum Tolerated Dose Middle Aged Remission Induction Stem Cell Factor - administration & dosage Stem Cell Factor - adverse effects Stem Cell Factor - pharmacology T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Treatment Outcome |
| title | A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer |
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