Antigen-specific immunity and tumor inflammation after vaccination with BPX-101, a drug-activated dendritic cell vaccine for metastatic castration-resistant prostate cancer (mCRPC).

Journal: J Clin Oncol 29: 2011 (suppl 7; abstr 176)

T. M. Wheeler, B. Zhao, G. Sonpavde, J. D. McMannis, Y. Bai, N. Lapteva, M. Seethammagari, J. M. Levitt, D. M. Spencer, K. M. Slawin; Department of Pathology, Baylor College of Medicine, Houston, TX; University of Texas Health Science Center at Houston, Houston, TX; Texas Oncology, Baylor College of Medicine, Houston, TX; University of Texas M. D. Anderson Cancer Center, Houston, TX; Memorial Hermann Hospital-Texas Medical Center, Houston, TX; Baylor College of Medicine, Houston, TX; Vanguard Urologic Institute, Houston, TX


Background: We report evidence of antigen-specific immunity and severe prostate cancer inflammation and necrosis after vaccination in patients enrolled in a phase I-IIa clinical trial of BPX-101, a drug-activated DC vaccine for mCRPC. Methods: Twelve men with progressive, mCRPC were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and activating agent AP1903. BPX-101, which targets prostate-specific membrane antigen (PSMA), was administered intradermally every 2 weeks for 6 doses, followed 24 hours after each dose by infusion of AP1903 (0.4 mg/kg). Injection site skin biopsies were performed after the fourth vaccination. T cells cultured from the skin biopsy ex vivo were stimulated with PSMA protein or control antigens, and were analyzed using Luminex microspheres for 30 inflammatory cytokines/chemokines. One patient (#1007) with an intact prostate developed lower urinary tract bleeding after the fifth vaccination and underwent a transurethral resection of bleeding prostate cancer tissue. Paraffin-embedded blocks were stained for hematoxylin and eosin (H&E). Immunohistochemical stains for CD3, CD4, CD8 and CD34 were also performed. Results: Of 5 subjects with evaluable injection site biopsy results, all exhibited PSMA-specific immunity (3 TH1-biased and 2 TH2- biased). Subject 1007’s injection site biopsy demonstrated a significant >10-fold increase in IFN-gamma and IL-2 after stimulation by PSMA, compared to stimulation by ovalbumin, consistent with induction of a strong PSMA-specific CTL or TH1-biased immune response. H&E stained resected prostate tissue demonstrated Gleason 8 (4+4) prostate adenocarcinoma exhibiting a severe inflammatory response, consisting of infiltrating plasma cells and CD4+ and CD8+ T cells. Large areas of necrosis were seen adjacent to inflamed prostate cancer tissue. Conclusions: Vaccination with BPX-101 followed by AP1903 can induce a strong, PSMA-specific immune response. Furthermore, evidence of severe prostate cancer-specific inflammation and necrosis, associated with a strong PSMA-specific immune response has been observed after multiple doses of BPX-101.