Cellular immunotherapy study of prostate cancer patients and resulting IgG responses to peptide epitopes predicted from prostate tumor-associated autoantigens
The immunogenicity of a cellular immunotherapy using genetically modified vaccines to express α(1,3)galactosyl epitopes (αGal) was evaluated in advanced prostate cancer (PC) patients. In this dose escalation phase I study, we report safety, feasibility, and immunologic data of an immunotherapy compo...
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| Veröffentlicht in: | Journal of immunotherapy (1997) 2013-01, Vol.36 (1), p.57-65 |
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| container_title | Journal of immunotherapy (1997) |
| container_volume | 36 |
| creator | Hemstreet, 3rd, George P Rossi, Gabriela R Pisarev, Vladimir M Enke, Charles A Helfner, Laura Hauke, Ralph J Tennant, Lucinda Ramsey, William Jay Vahanian, Nicholas N Link, Charles J |
| description | The immunogenicity of a cellular immunotherapy using genetically modified vaccines to express α(1,3)galactosyl epitopes (αGal) was evaluated in advanced prostate cancer (PC) patients. In this dose escalation phase I study, we report safety, feasibility, and immunologic data of an immunotherapy composed of 2 human PC cell lines engineered to express αGal epitopes (HyperAcute-Prostate, HAP, NewLink Genetics). Eight patients received up to 12 biweekly vaccinations with HAP. Enrolled patients (aged range, 53-85 y) had American Joint Committee on Cancer stage IV, any T, any N, M1, Eastern Cooperative Oncology Group PS≤2, at least 1 prior hormonal treatment and 100 d). In conclusion, HAP immunotherapy induces IgG responses to epitopes from autoantigens overexpressed in PC suggesting dose-dependent effect. HAP represents a viable immunotherapy approach to induce immune responses against tumor cells and may provide clinical benefit with minimal toxicity. |
| doi_str_mv | 10.1097/CJI.0b013e3182780abc |
| format | Article |
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In this dose escalation phase I study, we report safety, feasibility, and immunologic data of an immunotherapy composed of 2 human PC cell lines engineered to express αGal epitopes (HyperAcute-Prostate, HAP, NewLink Genetics). Eight patients received up to 12 biweekly vaccinations with HAP. Enrolled patients (aged range, 53-85 y) had American Joint Committee on Cancer stage IV, any T, any N, M1, Eastern Cooperative Oncology Group PS≤2, at least 1 prior hormonal treatment and <3 prior chemotherapies, adequate bone marrow and organ function, and albumin ≥3.0 g/dL. Serum IgG antibodies to synthetic peptides overexpressed in PC were determined by enzyme-linked immunosorbent assay. Results indicate that HAP immunotherapy induced humoral immune responses to autoantigens in 2 of 8 patients. These patients developed IgG antibody to multiple epitopes overexpressed in PC after immunization. These responding patients received higher doses of the immunotherapy suggesting a dose response. Two immunogenic proteins (prostate-specific membrane antigen, hepsin) belong to the extracellular molecules family participating in malignant cell invasion. Median overall survival for patients was 25.1 months with 1 patient surviving over 70 months with stable PSA and bone metastasis before expiring of other causes. Three of 8 patients showed PSA stabilization (>100 d). In conclusion, HAP immunotherapy induces IgG responses to epitopes from autoantigens overexpressed in PC suggesting dose-dependent effect. HAP represents a viable immunotherapy approach to induce immune responses against tumor cells and may provide clinical benefit with minimal toxicity.</description><identifier>ISSN: 1524-9557</identifier><identifier>EISSN: 1537-4513</identifier><identifier>DOI: 10.1097/CJI.0b013e3182780abc</identifier><identifier>PMID: 23211622</identifier><language>eng</language><publisher>United States</publisher><subject>Adenocarcinoma - blood ; Adenocarcinoma - immunology ; Adenocarcinoma - therapy ; Aged ; Aged, 80 and over ; Antigens, Neoplasm - immunology ; Autoantigens - immunology ; Cancer Vaccines ; Cell Line, Tumor ; Humans ; Immunoglobulin G - blood ; Immunotherapy ; Male ; Middle Aged ; Peptides - immunology ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - therapy ; Trisaccharides - immunology</subject><ispartof>Journal of immunotherapy (1997), 2013-01, Vol.36 (1), p.57-65</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-d55735d6745587f932da200c2f15487d977cdea6388ec272cd7955b8710120ad3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23211622$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hemstreet, 3rd, George P</creatorcontrib><creatorcontrib>Rossi, Gabriela R</creatorcontrib><creatorcontrib>Pisarev, Vladimir M</creatorcontrib><creatorcontrib>Enke, Charles A</creatorcontrib><creatorcontrib>Helfner, Laura</creatorcontrib><creatorcontrib>Hauke, Ralph J</creatorcontrib><creatorcontrib>Tennant, Lucinda</creatorcontrib><creatorcontrib>Ramsey, William Jay</creatorcontrib><creatorcontrib>Vahanian, Nicholas N</creatorcontrib><creatorcontrib>Link, Charles J</creatorcontrib><title>Cellular immunotherapy study of prostate cancer patients and resulting IgG responses to peptide epitopes predicted from prostate tumor-associated autoantigens</title><title>Journal of immunotherapy (1997)</title><addtitle>J Immunother</addtitle><description>The immunogenicity of a cellular immunotherapy using genetically modified vaccines to express α(1,3)galactosyl epitopes (αGal) was evaluated in advanced prostate cancer (PC) patients. In this dose escalation phase I study, we report safety, feasibility, and immunologic data of an immunotherapy composed of 2 human PC cell lines engineered to express αGal epitopes (HyperAcute-Prostate, HAP, NewLink Genetics). Eight patients received up to 12 biweekly vaccinations with HAP. Enrolled patients (aged range, 53-85 y) had American Joint Committee on Cancer stage IV, any T, any N, M1, Eastern Cooperative Oncology Group PS≤2, at least 1 prior hormonal treatment and <3 prior chemotherapies, adequate bone marrow and organ function, and albumin ≥3.0 g/dL. Serum IgG antibodies to synthetic peptides overexpressed in PC were determined by enzyme-linked immunosorbent assay. Results indicate that HAP immunotherapy induced humoral immune responses to autoantigens in 2 of 8 patients. These patients developed IgG antibody to multiple epitopes overexpressed in PC after immunization. These responding patients received higher doses of the immunotherapy suggesting a dose response. Two immunogenic proteins (prostate-specific membrane antigen, hepsin) belong to the extracellular molecules family participating in malignant cell invasion. Median overall survival for patients was 25.1 months with 1 patient surviving over 70 months with stable PSA and bone metastasis before expiring of other causes. Three of 8 patients showed PSA stabilization (>100 d). In conclusion, HAP immunotherapy induces IgG responses to epitopes from autoantigens overexpressed in PC suggesting dose-dependent effect. HAP represents a viable immunotherapy approach to induce immune responses against tumor cells and may provide clinical benefit with minimal toxicity.</description><subject>Adenocarcinoma - blood</subject><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - therapy</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Autoantigens - immunology</subject><subject>Cancer Vaccines</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>Immunoglobulin G - blood</subject><subject>Immunotherapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Peptides - immunology</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Trisaccharides - immunology</subject><issn>1524-9557</issn><issn>1537-4513</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUclu2zAQJYoGTeLkD4qCx16UcJFM6VgYbeIgQC7JWRiTI5eFRLJcDv6ZfmtpxE2AnmZ_M_MeIZ85u-FsULebh-0N2zEuUfJeqJ7BTn8gF7yTqmk7Lj8efdE2Q9epc3KZ0i_GxFq04hM5F1JwvhbigvzZ4DyXGSK1y1Kczz8xQjjQlIs5UD_REH3KkJFqcBojDZAtupwoOEMjpjJn6_Z0u787RsG7hIlmTwOGbA1SDDb7UHMhorE6o6FT9Ms7bi6Ljw2k5LWFYxlK9uCy3aNLV-Rsgjnh9cmuyMuP78-b--bx6W67-fbYaNmy3Jj6o-zMWrVd16tpkMKAYEyLiXdtr8yglDYIa9n3qIUS2qhKy65XnHHBwMgV-fqKW8_6XTDlcbFJV2rAoS9p5GKofPEKX1vb11ZdP0gRpzFEu0A8jJyNR2XGqsz4vzJ17MtpQ9ktaN6G_kkh_wLegY83</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>Hemstreet, 3rd, George P</creator><creator>Rossi, Gabriela R</creator><creator>Pisarev, Vladimir M</creator><creator>Enke, Charles A</creator><creator>Helfner, Laura</creator><creator>Hauke, Ralph J</creator><creator>Tennant, Lucinda</creator><creator>Ramsey, William Jay</creator><creator>Vahanian, Nicholas N</creator><creator>Link, Charles J</creator><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>7QP</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201301</creationdate><title>Cellular immunotherapy study of prostate cancer patients and resulting IgG responses to peptide epitopes predicted from prostate tumor-associated autoantigens</title><author>Hemstreet, 3rd, George P ; 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Two immunogenic proteins (prostate-specific membrane antigen, hepsin) belong to the extracellular molecules family participating in malignant cell invasion. Median overall survival for patients was 25.1 months with 1 patient surviving over 70 months with stable PSA and bone metastasis before expiring of other causes. Three of 8 patients showed PSA stabilization (>100 d). In conclusion, HAP immunotherapy induces IgG responses to epitopes from autoantigens overexpressed in PC suggesting dose-dependent effect. HAP represents a viable immunotherapy approach to induce immune responses against tumor cells and may provide clinical benefit with minimal toxicity.</abstract><cop>United States</cop><pmid>23211622</pmid><doi>10.1097/CJI.0b013e3182780abc</doi><tpages>9</tpages></addata></record> |
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| subjects | Adenocarcinoma - blood Adenocarcinoma - immunology Adenocarcinoma - therapy Aged Aged, 80 and over Antigens, Neoplasm - immunology Autoantigens - immunology Cancer Vaccines Cell Line, Tumor Humans Immunoglobulin G - blood Immunotherapy Male Middle Aged Peptides - immunology Prostatic Neoplasms - blood Prostatic Neoplasms - immunology Prostatic Neoplasms - therapy Trisaccharides - immunology |
| title | Cellular immunotherapy study of prostate cancer patients and resulting IgG responses to peptide epitopes predicted from prostate tumor-associated autoantigens |
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