Phase I neoadjuvant study of intravesical recombinant fowlpox-GM-CSF (rF-GM-CSF) or fowlpox-TRICOM (rF-TRICOM) in patients with bladder carcinoma
| العنوان: | Phase I neoadjuvant study of intravesical recombinant fowlpox-GM-CSF (rF-GM-CSF) or fowlpox-TRICOM (rF-TRICOM) in patients with bladder carcinoma |
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| المؤلفون: | Tina M. Mayer, Stephen P. Peters, Joseph Aisner, Howard Streicher, Seena C. Aisner, Daniella E Portal, Claude Monken, Michael P. Kane, Amal Mansour, Edmund C. Lattime, Mark N. Stein, Isaac Yi Kim, Jennifer Nishioka, Eric A. Singer, Janice M. Mehnert, Malgorzata Wojtowicz, James L. Gulley, Robert E. Weiss, Weichung Shih |
| المصدر: | Cancer gene therapy |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Fowlpox, Cancer Research, medicine.medical_treatment, Urinary Bladder, Article, Cystectomy, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Carcinoma, Animals, Humans, Medicine, Molecular Biology, Aged, Fowlpox virus, Bladder cancer, Dose-Response Relationship, Drug, business.industry, Carcinoma in situ, Granulocyte-Macrophage Colony-Stimulating Factor, Middle Aged, medicine.disease, Neoadjuvant Therapy, Recombinant Proteins, 3. Good health, Administration, Intravesical, 030104 developmental biology, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, business |
| الوصف: | Intravesical BCG is a highly effective treatment for high-grade nonmuscle invasive bladder cancer and carcinoma in situ (CIS); however, for patients who are either resistant or become unresponsive to BCG therapy there is a need for alternative treatment approaches. This study examined the safety and feasibility of intravesically administered recombinant fowlpox virus encoding GM-CSF (Arm A) or TRICOM (Arm B); and the local and systemic immunologic responses generated to the vector(s). Twenty bladder cancer patients scheduled for cystectomy as their standard of care received preoperatively four weekly doses of intravesical recombinant fowlpox. Treatment was well tolerated, however, three patients experienced transient elevations of liver transaminases, with one rising to the level of a DLT. Cystectomy derived tumor and normal bladder mucosa demonstrated mRNA for the virally encoded LacZ gene supporting effective infection/transfection. Detected serum antibody to the LacZ encoding β-galactosidase indicated successful expression of vector-encoding gene products and the ability to immunize via the bladder site. H&E and IHC using a panel of immune cell specific antigens demonstrated immune cell infiltration of the bladder wall. These findings demonstrate good safety profile, successful infection/transfection, ability to generate systemic immune response, and local recruitment of immune cell populations with intravesical administration of fowlpox-based constructs encoding for GM-CSF(rF-GM-CSF) or TRICOM (rF-TRICOM), and support further evaluation of this treatment modality for bladder cancer. |
| تدمد: | 1476-5500 0929-1903 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::156a272a01be8021f6a09ea331c877bd https://doi.org/10.1038/s41417-019-0112-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....156a272a01be8021f6a09ea331c877bd |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765500 09291903 |
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