title: Serial assessment of lymphocytes and apoptosis in the prostate during coordinated intraprostatic dendritic cell injection and radiotherapy.
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.
authors.affiliation: 21st Century Oncology Translational Research Consortium (TRC), Scottsdale, AZ 85251, USA. sfinkels@rtsx.com
authors.forename: Steven Eric
authors.initials: SE
authors.lastname: Finkelstein
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Mary
authors.initials: M
authors.lastname: Dunn
authors.forename: Mary-Jane
authors.initials: MJ
authors.lastname: Farmello
authors.forename: Renee
authors.initials: R
authors.lastname: Smilee
authors.forename: William
authors.initials: W
authors.lastname: Janssen
authors.forename: Loveleen
authors.initials: L
authors.lastname: Kang
authors.forename: Tian
authors.initials: T
authors.lastname: Chuang
authors.forename: John
authors.initials: J
authors.lastname: Seigne
authors.forename: Julio
authors.initials: J
authors.lastname: Pow-Sang
authors.forename: Javier F
authors.initials: JF
authors.lastname: Torres-Roca
authors.forename: Randy
authors.initials: R
authors.lastname: Heysek
authors.forename: Matt
authors.initials: M
authors.lastname: Biagoli
authors.forename: Ravi
authors.initials: R
authors.lastname: Shankar
authors.forename: Jacob
authors.initials: J
authors.lastname: Scott
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
authors.forename: Dmitry
authors.initials: D
authors.lastname: Gabrilovich
authors.forename: Mayer
authors.initials: M
authors.lastname: Fishman
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000637:transplantation; D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018655:Lymphocyte Count; D008297:Male; D011467:Prostate / Q000276:immunology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D011878:Radiotherapy; D016896:Treatment Outcome