Level of anti‐mouse‐antibody response induced by bi‐specific monoclonal antibody OC/TR in ovarian‐carcinoma patients is associated with longer survival
More than 60% of cancer patients injected with intact murine monoclonal antibody (MAb) develop a humoral response against the antigen even after a single dose. Analysis of a series of 35 ovarian‐cancer patients entered in phase‐I and ‐II clinical studies of T‐cells retargeted with the bi‐specific F(...
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| Veröffentlicht in: | International journal of cancer 1999-02, Vol.84 (1), p.62-68 |
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| container_title | International journal of cancer |
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| creator | Miotti, Silvia Negri, Donatella R.M. Valota, Olga Calabrese, Marcella Bolhuis, Reinder L.H. Gratama, Jan W. Colnaghi, Maria I. Canevari, Silvana |
| description | More than 60% of cancer patients injected with intact murine monoclonal antibody (MAb) develop a humoral response against the antigen even after a single dose. Analysis of a series of 35 ovarian‐cancer patients entered in phase‐I and ‐II clinical studies of T‐cells retargeted with the bi‐specific F(ab′)2 OC/TR revealed: (i) a detectable human anti‐mouse antibody (HAMA) response in 31/35 (88%) patients, with high HAMA levels (≥150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub‐group of non‐responder patients was considered. Evaluation of the anti‐idiotypic response in HAMA‐positive sera indicated that 11/17 sera showed high‐titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti‐CD3 parental MAbs to ovarian‐carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long‐lasting HAMA response maintained an anti‐idiotypic component, directed mainly against the αCD3 idiotype of bi‐MAb OC/TR in 2 out of 3 cases tested. Int. J. Cancer (Pred. Oncol.) 84:62–68, 1999. © 1999 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/(SICI)1097-0215(19990219)84:1<62::AID-IJC12>3.0.CO;2-T |
| format | Article |
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Analysis of a series of 35 ovarian‐cancer patients entered in phase‐I and ‐II clinical studies of T‐cells retargeted with the bi‐specific F(ab′)2 OC/TR revealed: (i) a detectable human anti‐mouse antibody (HAMA) response in 31/35 (88%) patients, with high HAMA levels (≥150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub‐group of non‐responder patients was considered. Evaluation of the anti‐idiotypic response in HAMA‐positive sera indicated that 11/17 sera showed high‐titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti‐CD3 parental MAbs to ovarian‐carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long‐lasting HAMA response maintained an anti‐idiotypic component, directed mainly against the αCD3 idiotype of bi‐MAb OC/TR in 2 out of 3 cases tested. Int. J. Cancer (Pred. Oncol.) 84:62–68, 1999. © 1999 Wiley‐Liss, Inc.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/(SICI)1097-0215(19990219)84:1<62::AID-IJC12>3.0.CO;2-T</identifier><identifier>PMID: 9988234</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Animals ; Antibodies, Anti-Idiotypic - biosynthesis ; Antibodies, Anti-Idiotypic - immunology ; Antibodies, Bispecific - immunology ; Antibodies, Bispecific - therapeutic use ; Antibodies, Heterophile - immunology ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers ; Female ; Humans ; Immunotherapy ; Medical sciences ; Mice ; Neoplasm Staging ; Ovarian Neoplasms - immunology ; Ovarian Neoplasms - therapy ; Pharmacology. 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Analysis of a series of 35 ovarian‐cancer patients entered in phase‐I and ‐II clinical studies of T‐cells retargeted with the bi‐specific F(ab′)2 OC/TR revealed: (i) a detectable human anti‐mouse antibody (HAMA) response in 31/35 (88%) patients, with high HAMA levels (≥150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub‐group of non‐responder patients was considered. Evaluation of the anti‐idiotypic response in HAMA‐positive sera indicated that 11/17 sera showed high‐titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti‐CD3 parental MAbs to ovarian‐carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long‐lasting HAMA response maintained an anti‐idiotypic component, directed mainly against the αCD3 idiotype of bi‐MAb OC/TR in 2 out of 3 cases tested. Int. J. Cancer (Pred. Oncol.) 84:62–68, 1999. © 1999 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Antibodies, Anti-Idiotypic - biosynthesis</subject><subject>Antibodies, Anti-Idiotypic - immunology</subject><subject>Antibodies, Bispecific - immunology</subject><subject>Antibodies, Bispecific - therapeutic use</subject><subject>Antibodies, Heterophile - immunology</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neoplasm Staging</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>Survival Rate</subject><subject>T-Lymphocytes - immunology</subject><subject>Time Factors</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O0zAUhSMEGsrAIyB5gdDMIh3bcey4oJFGGX6KKlWCAkvLdW7AKImLnXTU3TwCb8C78SQ4tJQFSKyu7Xvu8bG_JLkkeEowphdn7-bl_JxgKVJMSX5GpJRxIc8LNiPPOZ3NrubX6fxNSehlNsXTcvmMpqs7yeQ4cjeZRCOcCpLx-8mDEL5gTEiO2UlyImVR0IxNku8L2EKDXI1019sft99aNwSIddyuXbVDHsLGdQGQ7arBQIXWO7QelWEDxtbWoNZ1zjSu0w06Ti3Li9XbOILcVnuru6g32hvbuVajje4tdH1ANiAdgjNW99H4xvafUfT5BB6FwW_tVjcPk3u1bgI8OtTT5P3LF6vydbpYvpqXV4vUMEFpSgtCBSkYFZRxHh9MISeCVJnBWbUWNRUYIJMiZ5wRISjQCiThmhsJpooDp8nTve_Gu68DhF61NhhoGt1B_BHFZc5zzlkUftgLjXcheKjVxttW-50iWI3klBrJqRGDGjGo3-RUwRRRPAoiOfWLnMoUVuVSUbWKxo8PCYZ1C9XR9oAq9p8c-joY3dRed8aGP7fznEmaR9nHvezGNrD7K9z_sv0r2v4g-wmoO8Za</recordid><startdate>19990219</startdate><enddate>19990219</enddate><creator>Miotti, Silvia</creator><creator>Negri, Donatella R.M.</creator><creator>Valota, Olga</creator><creator>Calabrese, Marcella</creator><creator>Bolhuis, Reinder L.H.</creator><creator>Gratama, Jan W.</creator><creator>Colnaghi, Maria I.</creator><creator>Canevari, Silvana</creator><general>John Wiley & Sons, Inc</general><general>Wiley-Liss</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>7X8</scope></search><sort><creationdate>19990219</creationdate><title>Level of anti‐mouse‐antibody response induced by bi‐specific monoclonal antibody OC/TR in ovarian‐carcinoma patients is associated with longer survival</title><author>Miotti, Silvia ; Negri, Donatella R.M. ; Valota, Olga ; Calabrese, Marcella ; Bolhuis, Reinder L.H. ; Gratama, Jan W. ; Colnaghi, Maria I. ; Canevari, Silvana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4722-281271842724661362e5171d3c03db7f270ee39754641772e2de916a6c9ecd613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Antibodies, Anti-Idiotypic - biosynthesis</topic><topic>Antibodies, Anti-Idiotypic - immunology</topic><topic>Antibodies, Bispecific - immunology</topic><topic>Antibodies, Bispecific - therapeutic use</topic><topic>Antibodies, Heterophile - immunology</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Neoplasm Staging</topic><topic>Ovarian Neoplasms - immunology</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>Survival Rate</topic><topic>T-Lymphocytes - immunology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miotti, Silvia</creatorcontrib><creatorcontrib>Negri, Donatella R.M.</creatorcontrib><creatorcontrib>Valota, Olga</creatorcontrib><creatorcontrib>Calabrese, Marcella</creatorcontrib><creatorcontrib>Bolhuis, Reinder L.H.</creatorcontrib><creatorcontrib>Gratama, Jan W.</creatorcontrib><creatorcontrib>Colnaghi, Maria I.</creatorcontrib><creatorcontrib>Canevari, Silvana</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>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miotti, Silvia</au><au>Negri, Donatella R.M.</au><au>Valota, Olga</au><au>Calabrese, Marcella</au><au>Bolhuis, Reinder L.H.</au><au>Gratama, Jan W.</au><au>Colnaghi, Maria I.</au><au>Canevari, Silvana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Level of anti‐mouse‐antibody response induced by bi‐specific monoclonal antibody OC/TR in ovarian‐carcinoma patients is associated with longer survival</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>1999-02-19</date><risdate>1999</risdate><volume>84</volume><issue>1</issue><spage>62</spage><epage>68</epage><pages>62-68</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>More than 60% of cancer patients injected with intact murine monoclonal antibody (MAb) develop a humoral response against the antigen even after a single dose. Analysis of a series of 35 ovarian‐cancer patients entered in phase‐I and ‐II clinical studies of T‐cells retargeted with the bi‐specific F(ab′)2 OC/TR revealed: (i) a detectable human anti‐mouse antibody (HAMA) response in 31/35 (88%) patients, with high HAMA levels (≥150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub‐group of non‐responder patients was considered. Evaluation of the anti‐idiotypic response in HAMA‐positive sera indicated that 11/17 sera showed high‐titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti‐CD3 parental MAbs to ovarian‐carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long‐lasting HAMA response maintained an anti‐idiotypic component, directed mainly against the αCD3 idiotype of bi‐MAb OC/TR in 2 out of 3 cases tested. Int. J. Cancer (Pred. Oncol.) 84:62–68, 1999. © 1999 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>9988234</pmid><doi>10.1002/(SICI)1097-0215(19990219)84:1<62::AID-IJC12>3.0.CO;2-T</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Anti-Idiotypic - biosynthesis Antibodies, Anti-Idiotypic - immunology Antibodies, Bispecific - immunology Antibodies, Bispecific - therapeutic use Antibodies, Heterophile - immunology Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use Antineoplastic agents Biological and medical sciences Biomarkers Female Humans Immunotherapy Medical sciences Mice Neoplasm Staging Ovarian Neoplasms - immunology Ovarian Neoplasms - therapy Pharmacology. Drug treatments Prognosis Survival Rate T-Lymphocytes - immunology Time Factors |
| title | Level of anti‐mouse‐antibody response induced by bi‐specific monoclonal antibody OC/TR in ovarian‐carcinoma patients is associated with longer survival |
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