Serial assessment of lymphocytes and apoptosis in the prostate during coordinated intraprostatic dendritic cell injection and radiotherapy

Author:

Finkelstein Steven Eric1,Rodriguez Francisco2,Dunn Mary3,Farmello Mary-Jane4,Smilee Renee4,Janssen William4,Kang Loveleen5,Chuang Tian6,Seigne John7,Pow-Sang Julio8,Torres-Roca Javier F9,Heysek Randy9,Biagoli Matt9,Shankar Ravi9,Scott Jacob9,Antonia Scott10,Gabrilovich Dmitry11,Fishman Mayer8

Affiliation:

1. 21st Century Oncology Translational Research Consortium (TRC), 7340 E Thomas Rd, Scottsdale, AZ, 85251, USA and Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

2. Florida Cancer Specialists, Fort Myers, FL, USA

3. Clinical Trial Support, Moffitt Cancer Center, Tampa, FL, USA

4. Cell Therapy Facility, Moffitt Cancer Center, Tampa, FL, USA

5. Department of Pathology, James A Haley VA MC, Tampa, FL, USA

6. Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA

7. Urology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

8. Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA

9. Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA

10. Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA

11. Section of Dendritic Cell Biology, Moffitt Cancer Center, Tampa, FL, USA

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.

Publisher

Future Medicine Ltd

Subject

Oncology,Immunology,Immunology and Allergy

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