Loading…
Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia
The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20...
Saved in:
Published in: | Molecular cancer 2011-04, Vol.10 (1), p.42-42, Article 42 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323 |
---|---|
cites | cdi_FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323 |
container_end_page | 42 |
container_issue | 1 |
container_start_page | 42 |
container_title | Molecular cancer |
container_volume | 10 |
creator | Loisel, Séverine André, Pierre-Alain Golay, Josee Buchegger, Franz Kadouche, Jean Cérutti, Martine Bologna, Luca Kosinski, Marek Viertl, David Delaloye, Angelika Bischof Berthou, Christian Mach, Jean-Pierre Boumsell, Laurence |
description | The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells.
The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5.
Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential. |
doi_str_mv | 10.1186/1476-4598-10-42 |
format | article |
fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_bd95c36aeb824bf08e602273beb84d10</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A257470411</galeid><doaj_id>oai_doaj_org_article_bd95c36aeb824bf08e602273beb84d10</doaj_id><sourcerecordid>A257470411</sourcerecordid><originalsourceid>FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323</originalsourceid><addsrcrecordid>eNp1kk1v1DAQhiMEoqVw5oYsceBCWn_m44K0rYBWWokLnC07Hu-6JPZiJ1X7B_jdOE1ZdVGRD7ZmnvfNZGaK4i3Bp4Q01RnhdVVy0TYlwSWnz4rjfeT5o_dR8Sqla4xJ3dT8ZXFEicBc1O1x8XvlRzdOQ5giAmuhGxMKFiXnNz2gEFEXBu08GDQEH7o-eNUjlTU6GAcJGRezJqfVRjmfRjTAoKPycA9twCcEt7sIKWVG36HtNCiPzlEHfZ9QD9NPBYNTr4sXVvUJ3jzcJ8WPL5-_X1yW629fry5W61JXlIwlM0ZUoLmtai5wQwkXtuUEC4xb2rTQiPw2tFOGU8aNUgxrywxhnCmMGWUnxdXia4K6lrvoBhXvZFBO3gdC3EgVR9f1ILVpRccqBbqhXFvcQIUprZnOAW4Izl6fFq_dpAcwHfgxqv7A9DDj3VZuwo1kWcyrJht8XAy2_8guV2uZmwlxkBiLthKM3pCMny-4duE_3zvM5NHJeQXkvAKSYMnnBnx4KDqGXxOkUQ4uzcPIIwtTkk3Viho3dZvJ9wu5UbkbztuQTbuZlisqal5jTuaiTp-g8jF5rF3wYF2OHwjOFkEXQ0oR7P4HcoHzTj9R8rvHfd7zf5eY_QES4vKU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>869570879</pqid></control><display><type>article</type><title>Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia</title><source>Open Access: PubMed Central</source><source>Publicly Available Content (ProQuest)</source><creator>Loisel, Séverine ; André, Pierre-Alain ; Golay, Josee ; Buchegger, Franz ; Kadouche, Jean ; Cérutti, Martine ; Bologna, Luca ; Kosinski, Marek ; Viertl, David ; Delaloye, Angelika Bischof ; Berthou, Christian ; Mach, Jean-Pierre ; Boumsell, Laurence</creator><creatorcontrib>Loisel, Séverine ; André, Pierre-Alain ; Golay, Josee ; Buchegger, Franz ; Kadouche, Jean ; Cérutti, Martine ; Bologna, Luca ; Kosinski, Marek ; Viertl, David ; Delaloye, Angelika Bischof ; Berthou, Christian ; Mach, Jean-Pierre ; Boumsell, Laurence</creatorcontrib><description>The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells.
The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5.
Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential.</description><identifier>ISSN: 1476-4598</identifier><identifier>EISSN: 1476-4598</identifier><identifier>DOI: 10.1186/1476-4598-10-42</identifier><identifier>PMID: 21504579</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Animals ; Antibodies, Monoclonal - pharmacology ; Antibody-Dependent Cell Cytotoxicity - immunology ; Antigens, Surface - immunology ; Antineoplastic Agents - pharmacology ; B cells ; Biochemistry, Molecular Biology ; Cancer ; Care and treatment ; Cell Line, Tumor ; Complement Activation - drug effects ; Complement Activation - immunology ; Genomics ; Health aspects ; Humans ; Iodine Radioisotopes ; Leukemia ; Leukemia, B-Cell - physiopathology ; Life Sciences ; Lymphoma - physiopathology ; Macrophages - drug effects ; Macrophages - immunology ; Mice ; Mice, SCID ; Monoclonal antibodies ; Phagocytosis - drug effects ; Phagocytosis - immunology ; Physiological aspects ; Protein Binding ; Survival Analysis ; Tumor antigens ; Xenograft Model Antitumor Assays</subject><ispartof>Molecular cancer, 2011-04, Vol.10 (1), p.42-42, Article 42</ispartof><rights>COPYRIGHT 2011 BioMed Central Ltd.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright ©2011 Loisel et al; licensee BioMed Central Ltd. 2011 Loisel et al; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323</citedby><cites>FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103468/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103468/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,37013,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21504579$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-00596532$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Loisel, Séverine</creatorcontrib><creatorcontrib>André, Pierre-Alain</creatorcontrib><creatorcontrib>Golay, Josee</creatorcontrib><creatorcontrib>Buchegger, Franz</creatorcontrib><creatorcontrib>Kadouche, Jean</creatorcontrib><creatorcontrib>Cérutti, Martine</creatorcontrib><creatorcontrib>Bologna, Luca</creatorcontrib><creatorcontrib>Kosinski, Marek</creatorcontrib><creatorcontrib>Viertl, David</creatorcontrib><creatorcontrib>Delaloye, Angelika Bischof</creatorcontrib><creatorcontrib>Berthou, Christian</creatorcontrib><creatorcontrib>Mach, Jean-Pierre</creatorcontrib><creatorcontrib>Boumsell, Laurence</creatorcontrib><title>Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia</title><title>Molecular cancer</title><addtitle>Mol Cancer</addtitle><description>The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells.
The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5.
Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibody-Dependent Cell Cytotoxicity - immunology</subject><subject>Antigens, Surface - immunology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>B cells</subject><subject>Biochemistry, Molecular Biology</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Complement Activation - drug effects</subject><subject>Complement Activation - immunology</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Iodine Radioisotopes</subject><subject>Leukemia</subject><subject>Leukemia, B-Cell - physiopathology</subject><subject>Life Sciences</subject><subject>Lymphoma - physiopathology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Monoclonal antibodies</subject><subject>Phagocytosis - drug effects</subject><subject>Phagocytosis - immunology</subject><subject>Physiological aspects</subject><subject>Protein Binding</subject><subject>Survival Analysis</subject><subject>Tumor antigens</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1476-4598</issn><issn>1476-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNp1kk1v1DAQhiMEoqVw5oYsceBCWn_m44K0rYBWWokLnC07Hu-6JPZiJ1X7B_jdOE1ZdVGRD7ZmnvfNZGaK4i3Bp4Q01RnhdVVy0TYlwSWnz4rjfeT5o_dR8Sqla4xJ3dT8ZXFEicBc1O1x8XvlRzdOQ5giAmuhGxMKFiXnNz2gEFEXBu08GDQEH7o-eNUjlTU6GAcJGRezJqfVRjmfRjTAoKPycA9twCcEt7sIKWVG36HtNCiPzlEHfZ9QD9NPBYNTr4sXVvUJ3jzcJ8WPL5-_X1yW629fry5W61JXlIwlM0ZUoLmtai5wQwkXtuUEC4xb2rTQiPw2tFOGU8aNUgxrywxhnCmMGWUnxdXia4K6lrvoBhXvZFBO3gdC3EgVR9f1ILVpRccqBbqhXFvcQIUprZnOAW4Izl6fFq_dpAcwHfgxqv7A9DDj3VZuwo1kWcyrJht8XAy2_8guV2uZmwlxkBiLthKM3pCMny-4duE_3zvM5NHJeQXkvAKSYMnnBnx4KDqGXxOkUQ4uzcPIIwtTkk3Viho3dZvJ9wu5UbkbztuQTbuZlisqal5jTuaiTp-g8jF5rF3wYF2OHwjOFkEXQ0oR7P4HcoHzTj9R8rvHfd7zf5eY_QES4vKU</recordid><startdate>20110419</startdate><enddate>20110419</enddate><creator>Loisel, Séverine</creator><creator>André, Pierre-Alain</creator><creator>Golay, Josee</creator><creator>Buchegger, Franz</creator><creator>Kadouche, Jean</creator><creator>Cérutti, Martine</creator><creator>Bologna, Luca</creator><creator>Kosinski, Marek</creator><creator>Viertl, David</creator><creator>Delaloye, Angelika Bischof</creator><creator>Berthou, Christian</creator><creator>Mach, Jean-Pierre</creator><creator>Boumsell, Laurence</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</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>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110419</creationdate><title>Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia</title><author>Loisel, Séverine ; André, Pierre-Alain ; Golay, Josee ; Buchegger, Franz ; Kadouche, Jean ; Cérutti, Martine ; Bologna, Luca ; Kosinski, Marek ; Viertl, David ; Delaloye, Angelika Bischof ; Berthou, Christian ; Mach, Jean-Pierre ; Boumsell, Laurence</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibody-Dependent Cell Cytotoxicity - immunology</topic><topic>Antigens, Surface - immunology</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>B cells</topic><topic>Biochemistry, Molecular Biology</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Complement Activation - drug effects</topic><topic>Complement Activation - immunology</topic><topic>Genomics</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Iodine Radioisotopes</topic><topic>Leukemia</topic><topic>Leukemia, B-Cell - physiopathology</topic><topic>Life Sciences</topic><topic>Lymphoma - physiopathology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Monoclonal antibodies</topic><topic>Phagocytosis - drug effects</topic><topic>Phagocytosis - immunology</topic><topic>Physiological aspects</topic><topic>Protein Binding</topic><topic>Survival Analysis</topic><topic>Tumor antigens</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Loisel, Séverine</creatorcontrib><creatorcontrib>André, Pierre-Alain</creatorcontrib><creatorcontrib>Golay, Josee</creatorcontrib><creatorcontrib>Buchegger, Franz</creatorcontrib><creatorcontrib>Kadouche, Jean</creatorcontrib><creatorcontrib>Cérutti, Martine</creatorcontrib><creatorcontrib>Bologna, Luca</creatorcontrib><creatorcontrib>Kosinski, Marek</creatorcontrib><creatorcontrib>Viertl, David</creatorcontrib><creatorcontrib>Delaloye, Angelika Bischof</creatorcontrib><creatorcontrib>Berthou, Christian</creatorcontrib><creatorcontrib>Mach, Jean-Pierre</creatorcontrib><creatorcontrib>Boumsell, Laurence</creatorcontrib><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><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Molecular cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Loisel, Séverine</au><au>André, Pierre-Alain</au><au>Golay, Josee</au><au>Buchegger, Franz</au><au>Kadouche, Jean</au><au>Cérutti, Martine</au><au>Bologna, Luca</au><au>Kosinski, Marek</au><au>Viertl, David</au><au>Delaloye, Angelika Bischof</au><au>Berthou, Christian</au><au>Mach, Jean-Pierre</au><au>Boumsell, Laurence</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia</atitle><jtitle>Molecular cancer</jtitle><addtitle>Mol Cancer</addtitle><date>2011-04-19</date><risdate>2011</risdate><volume>10</volume><issue>1</issue><spage>42</spage><epage>42</epage><pages>42-42</pages><artnum>42</artnum><issn>1476-4598</issn><eissn>1476-4598</eissn><abstract>The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells.
The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5.
Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>21504579</pmid><doi>10.1186/1476-4598-10-42</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1476-4598 |
ispartof | Molecular cancer, 2011-04, Vol.10 (1), p.42-42, Article 42 |
issn | 1476-4598 1476-4598 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_bd95c36aeb824bf08e602273beb84d10 |
source | Open Access: PubMed Central; Publicly Available Content (ProQuest) |
subjects | Analysis Animals Antibodies, Monoclonal - pharmacology Antibody-Dependent Cell Cytotoxicity - immunology Antigens, Surface - immunology Antineoplastic Agents - pharmacology B cells Biochemistry, Molecular Biology Cancer Care and treatment Cell Line, Tumor Complement Activation - drug effects Complement Activation - immunology Genomics Health aspects Humans Iodine Radioisotopes Leukemia Leukemia, B-Cell - physiopathology Life Sciences Lymphoma - physiopathology Macrophages - drug effects Macrophages - immunology Mice Mice, SCID Monoclonal antibodies Phagocytosis - drug effects Phagocytosis - immunology Physiological aspects Protein Binding Survival Analysis Tumor antigens Xenograft Model Antitumor Assays |
title | Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T23%3A24%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Antitumour%20effects%20of%20single%20or%20combined%20monoclonal%20antibodies%20directed%20against%20membrane%20antigens%20expressed%20by%20human%20B%20cells%20leukaemia&rft.jtitle=Molecular%20cancer&rft.au=Loisel,%20S%C3%A9verine&rft.date=2011-04-19&rft.volume=10&rft.issue=1&rft.spage=42&rft.epage=42&rft.pages=42-42&rft.artnum=42&rft.issn=1476-4598&rft.eissn=1476-4598&rft_id=info:doi/10.1186/1476-4598-10-42&rft_dat=%3Cgale_doaj_%3EA257470411%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-b621t-3dd56eb4f6745082145f94105009289e85105d2cad4234daa30bf3d1343a00323%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=869570879&rft_id=info:pmid/21504579&rft_galeid=A257470411&rfr_iscdi=true |