Transforming the prostatic tumor microenvironment with oncolytic virotherapy
Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prost...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-07-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1445459 |
| _version_ | 1811339426725363712 |
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| author | Matthew J. Atherton Kyle B. Stephenson Fanny Tzelepis David Bakhshinyan Jake K. Nikota Hwan Hee Son Anna Jirovec Charles Lefebvre Anna Dvorkin-Gheva Ali A. Ashkar Yonghong Wan David F. Stojdl Eric C. Belanger Rodney H. Breau John C. Bell Fred Saad Sheila K. Singh Jean-Simone Diallo Brian D. Lichty |
| author_facet | Matthew J. Atherton Kyle B. Stephenson Fanny Tzelepis David Bakhshinyan Jake K. Nikota Hwan Hee Son Anna Jirovec Charles Lefebvre Anna Dvorkin-Gheva Ali A. Ashkar Yonghong Wan David F. Stojdl Eric C. Belanger Rodney H. Breau John C. Bell Fred Saad Sheila K. Singh Jean-Simone Diallo Brian D. Lichty |
| author_sort | Matthew J. Atherton |
| collection | DOAJ |
| description | Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa. |
| first_indexed | 2024-04-13T18:26:26Z |
| format | Article |
| id | doaj.art-44bc5ab425ff4979b88e6403354f4852 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-13T18:26:26Z |
| publishDate | 2018-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-44bc5ab425ff4979b88e6403354f48522022-12-22T02:35:14ZengTaylor & Francis GroupOncoImmunology2162-402X2018-07-017710.1080/2162402X.2018.14454591445459Transforming the prostatic tumor microenvironment with oncolytic virotherapyMatthew J. Atherton0Kyle B. Stephenson1Fanny Tzelepis2David Bakhshinyan3Jake K. Nikota4Hwan Hee Son5Anna Jirovec6Charles Lefebvre7Anna Dvorkin-Gheva8Ali A. Ashkar9Yonghong Wan10David F. Stojdl11Eric C. Belanger12Rodney H. Breau13John C. Bell14Fred Saad15Sheila K. Singh16Jean-Simone Diallo17Brian D. Lichty18McMaster UniversityTurnstone BiologicsThe Ottawa Hospital Research InstituteMcMaster Stem Cell and Cancer Research Institute, McMaster UniversityTurnstone BiologicsThe Ottawa Hospital Research InstituteThe Ottawa Hospital Research InstituteCHEO Research Institute, Children's Hospital of Eastern OntarioMcMaster UniversityMcMaster UniversityMcMaster UniversityTurnstone BiologicsUniversity of OttawaThe Ottawa HospitalTurnstone BiologicsCentre Hospitalier de l'Université de Montréal (CHUM)McMaster Stem Cell and Cancer Research Institute, McMaster UniversityThe Ottawa Hospital Research InstituteMcMaster UniversityProstate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa.http://dx.doi.org/10.1080/2162402X.2018.1445459mg1-marabaprostatic carcinomavaccinationtumor microenvironmentsteap |
| spellingShingle | Matthew J. Atherton Kyle B. Stephenson Fanny Tzelepis David Bakhshinyan Jake K. Nikota Hwan Hee Son Anna Jirovec Charles Lefebvre Anna Dvorkin-Gheva Ali A. Ashkar Yonghong Wan David F. Stojdl Eric C. Belanger Rodney H. Breau John C. Bell Fred Saad Sheila K. Singh Jean-Simone Diallo Brian D. Lichty Transforming the prostatic tumor microenvironment with oncolytic virotherapy OncoImmunology mg1-maraba prostatic carcinoma vaccination tumor microenvironment steap |
| title | Transforming the prostatic tumor microenvironment with oncolytic virotherapy |
| title_full | Transforming the prostatic tumor microenvironment with oncolytic virotherapy |
| title_fullStr | Transforming the prostatic tumor microenvironment with oncolytic virotherapy |
| title_full_unstemmed | Transforming the prostatic tumor microenvironment with oncolytic virotherapy |
| title_short | Transforming the prostatic tumor microenvironment with oncolytic virotherapy |
| title_sort | transforming the prostatic tumor microenvironment with oncolytic virotherapy |
| topic | mg1-maraba prostatic carcinoma vaccination tumor microenvironment steap |
| url | http://dx.doi.org/10.1080/2162402X.2018.1445459 |
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