Abstract |
Local radiotherapy plus intratumoral syngeneic dendritic cell injection can mediate apoptosis/cell death and immunological tumor eradication in murine models. A novel method of coordinated intraprostatic, autologous dendritic cell injection together with radiation therapy was prospectively evaluated in five HLA-A2(+) subjects with high-risk, localized prostate cancer, using androgen suppression, 45 Gy external beam radiation therapy in 25 fractions over 5 weeks, dendritic cell injections after fractions 5, 15 and 25 and then interstitial radioactive seed placement. Serial prostate biopsies before and during treatment showed increased apoptotic cells and parenchymal distribution of CD8(+) cells. CD8(+) T-cell responses to test peptides were assessed using an enzyme-linked immunosorbent spot IFN-γ production assay, demonstrating some prostate cancer-specific protein-derived peptides associated with increased titer. In conclusion, the technique was feasible and well-tolerated and specific immune responses were observable. Future trials could further test the utility of this approach and improve on temporal coordination of intratumoral dendritic cell introduction with particular timelines of therapy-induced apoptosis.
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Authors | Steven Eric Finkelstein, Francisco Rodriguez, Mary Dunn, Mary-Jane Farmello, Renee Smilee, William Janssen, Loveleen Kang, Tian Chuang, John Seigne, Julio Pow-Sang, Javier F Torres-Roca, Randy Heysek, Matt Biagoli, Ravi Shankar, Jacob Scott, Scott Antonia, Dmitry Gabrilovich, Mayer Fishman |
Journal | Immunotherapy
(Immunotherapy)
Vol. 4
Issue 4
Pg. 373-82
(Apr 2012)
ISSN: 1750-7448 [Electronic] England |
PMID | 22512631
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Adult
- Antigen-Presenting Cells
(immunology, transplantation)
- Apoptosis
(physiology)
- CD4-Positive T-Lymphocytes
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Dendritic Cells
(immunology, transplantation)
- Humans
- Immunotherapy, Adoptive
(methods)
- Lymphocyte Count
- Male
- Prostate
(immunology, pathology)
- Prostatic Neoplasms
(immunology, pathology, radiotherapy, therapy)
- Radiotherapy
- Treatment Outcome
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