FOCUS on FOCIS: Combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer
Abstract Immunotherapy has emerged as another treatment modality in cancer. The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combi...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2009-04, Vol.131 (1), p.1-10 |
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| creator | Rožková, Daniela Tišerová, Hana Fučíková, Jitka Lašt'ovička, Jan Podrazil, Michal Ulčová, Hana Budínský, Vít Prausová, Jana Linke, Zdeněk Minárik, Ivo Šedivá, Anna Špíšek, Radek Bartůňková, Jiřina |
| description | Abstract Immunotherapy has emerged as another treatment modality in cancer. The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%. |
| doi_str_mv | 10.1016/j.clim.2009.01.001 |
| format | Article |
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The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2009.01.001</identifier><identifier>PMID: 19201656</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Adenocarcinoma - secondary ; Adenocarcinoma - therapy ; Aged ; Allergy and Immunology ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Bone Neoplasms - secondary ; Bone Neoplasms - therapy ; Cancer immunotherapy ; Chemo-immunotherapy ; Combined Modality Therapy ; Dendritic cells ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gynecology. Andrology. Obstetrics ; Humans ; Immunotherapy - methods ; Male ; Male genital diseases ; Medical sciences ; Neoplasms, Hormone-Dependent - secondary ; Neoplasms, Hormone-Dependent - therapy ; Nephrology. Urinary tract diseases ; Prostate cancer ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - therapy ; PSA ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland</subject><ispartof>Clinical immunology (Orlando, Fla.), 2009-04, Vol.131 (1), p.1-10</ispartof><rights>Elsevier Inc.</rights><rights>2009 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-5473224dd8682ef42456e5d4e24d6dcb924d2b4b93fa17a154187e63467c2a683</citedby><cites>FETCH-LOGICAL-c470t-5473224dd8682ef42456e5d4e24d6dcb924d2b4b93fa17a154187e63467c2a683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2009.01.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21378394$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19201656$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rožková, Daniela</creatorcontrib><creatorcontrib>Tišerová, Hana</creatorcontrib><creatorcontrib>Fučíková, Jitka</creatorcontrib><creatorcontrib>Lašt'ovička, Jan</creatorcontrib><creatorcontrib>Podrazil, Michal</creatorcontrib><creatorcontrib>Ulčová, Hana</creatorcontrib><creatorcontrib>Budínský, Vít</creatorcontrib><creatorcontrib>Prausová, Jana</creatorcontrib><creatorcontrib>Linke, Zdeněk</creatorcontrib><creatorcontrib>Minárik, Ivo</creatorcontrib><creatorcontrib>Šedivá, Anna</creatorcontrib><creatorcontrib>Špíšek, Radek</creatorcontrib><creatorcontrib>Bartůňková, Jiřina</creatorcontrib><title>FOCUS on FOCIS: Combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Abstract Immunotherapy has emerged as another treatment modality in cancer. The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%.</description><subject>Adenocarcinoma - secondary</subject><subject>Adenocarcinoma - therapy</subject><subject>Aged</subject><subject>Allergy and Immunology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bone Neoplasms - secondary</subject><subject>Bone Neoplasms - therapy</subject><subject>Cancer immunotherapy</subject><subject>Chemo-immunotherapy</subject><subject>Combined Modality Therapy</subject><subject>Dendritic cells</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunotherapy - methods</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>Medical sciences</subject><subject>Neoplasms, Hormone-Dependent - secondary</subject><subject>Neoplasms, Hormone-Dependent - therapy</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - therapy</subject><subject>PSA</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkt-L1DAQx4so3g_9B3yQvOhb6yRN01bkQJY7PTi4h_WeQ5pO2aybZE1SYf97U7Yo-KBP8yV8ZiYz3ymKNxQqClR82Ff6YGzFAPoKaAVAnxWXtGG0bKFunq9aCCouiqsY9wDQMCZeFhe0Z7lAIy4Lf_e4edoS70gW99uPZOPtYByORO_Q-tJYOzufdhjU8UQmH0jWJAVUyaJLxE9k54P1DsuAU1A6-XAiFpOKSSWjyTH4RSHRymkMr4oXkzpEfL3G6-Lp7vbb5mv58PjlfvP5odS8hVQ2vK0Z4-PYiY7hxBlvBDYjx_wmRj30ObKBD309Kdoq2nDatShqLlrNlOjq6-L9uW7u_2PGmKQ1UePhoBz6OUrRUmhA1P8FGfCWd7CA7AzqPFHMw8pjMFaFk6QgFz_kXi5-yMUPCVRmP3LS27X6PFgc_6SsBmTg3QqoqNUhb9BpE39zjNZtV_c8c5_OHOal_TQYZNQG80ZHE1AnOXrz73_c_JWeEWdyx-94wrj3c3DZDkllZBLkdrmc5XCgz0eTN1D_ApUqvTo</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Rožková, Daniela</creator><creator>Tišerová, Hana</creator><creator>Fučíková, Jitka</creator><creator>Lašt'ovička, Jan</creator><creator>Podrazil, Michal</creator><creator>Ulčová, Hana</creator><creator>Budínský, Vít</creator><creator>Prausová, Jana</creator><creator>Linke, Zdeněk</creator><creator>Minárik, Ivo</creator><creator>Šedivá, Anna</creator><creator>Špíšek, Radek</creator><creator>Bartůňková, Jiřina</creator><general>Elsevier Inc</general><general>Elsevier</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20090401</creationdate><title>FOCUS on FOCIS: Combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer</title><author>Rožková, Daniela ; Tišerová, Hana ; Fučíková, Jitka ; Lašt'ovička, Jan ; Podrazil, Michal ; Ulčová, Hana ; Budínský, Vít ; Prausová, Jana ; Linke, Zdeněk ; Minárik, Ivo ; Šedivá, Anna ; Špíšek, Radek ; Bartůňková, Jiřina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-5473224dd8682ef42456e5d4e24d6dcb924d2b4b93fa17a154187e63467c2a683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenocarcinoma - secondary</topic><topic>Adenocarcinoma - therapy</topic><topic>Aged</topic><topic>Allergy and Immunology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Bone Neoplasms - secondary</topic><topic>Bone Neoplasms - therapy</topic><topic>Cancer immunotherapy</topic><topic>Chemo-immunotherapy</topic><topic>Combined Modality Therapy</topic><topic>Dendritic cells</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunotherapy - methods</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>Neoplasms, Hormone-Dependent - secondary</topic><topic>Neoplasms, Hormone-Dependent - therapy</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - therapy</topic><topic>PSA</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. 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The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19201656</pmid><doi>10.1016/j.clim.2009.01.001</doi><tpages>10</tpages></addata></record> |
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| subjects | Adenocarcinoma - secondary Adenocarcinoma - therapy Aged Allergy and Immunology Antineoplastic Agents - therapeutic use Biological and medical sciences Bone Neoplasms - secondary Bone Neoplasms - therapy Cancer immunotherapy Chemo-immunotherapy Combined Modality Therapy Dendritic cells Fundamental and applied biological sciences. Psychology Fundamental immunology Gynecology. Andrology. Obstetrics Humans Immunotherapy - methods Male Male genital diseases Medical sciences Neoplasms, Hormone-Dependent - secondary Neoplasms, Hormone-Dependent - therapy Nephrology. Urinary tract diseases Prostate cancer Prostatic Neoplasms - pathology Prostatic Neoplasms - therapy PSA Tumors Tumors of the urinary system Urinary tract. Prostate gland |
| title | FOCUS on FOCIS: Combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer |
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