Abstract LB-80: Correlation of serum cytokines with clinical responses in patients treated with BPX-101, a novel dendritic cell vaccine for metastatic castration resistant prostate cancer (mCRPC)
Authors: Sonpavde Guru , McMannis John D. , Bai Yu , Rios Adan , Lapteva Natalia , Spencer David M. , Slawin Kevin M. 
Published: February 2011

Abstract
Background: We report interim clinical and immune monitoring results for the low dose cohort of patients enrolled in an ongoing Phase I/IIa clinical trial of BPX-101, a novel, autologous dendritic cell (DC) vaccine for mCRPC based on AP1903-inducible, iCD40-expressing DCs.
Methods: Men with progressive mCRPC were enrolled in a 3+3 dose escalation Phase I/IIa trial evaluating BPX-101 and AP1903. BPX-101 is produced from a single leukapheresis procedure by elutriation, differentiation of monocytes into DCs, transduction with Ad5f35-inducible human (ih)-CD40, antigen loading with a form of Prostate Specific Membrane Antigen (PSMA), and pre-activation with lipopolysaccharide and activating agent, AP1903. BPX-101 was administered intradermally every 2 weeks for 6 doses. AP1903 (0.4 mg/kg) was infused 24 hours after each BPX-101 dose. Blood samples were collected weekly, cryopreserved and batched for immune monitoring assays after completion of the first 12-weeks of therapy. IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-12, GMCSF, TNFα, IFNγ, IP-10, MCP-1, MIP-1α, MIP-1ß, and RANTES levels were evaluated, using a LINCOplex Immunoassay Panel.
Results: Of six subjects enrolled to date, three patients enrolled in the low dose cohort (4 × 106 cells) have completed at least 12 weeks of therapy (median 23, range 22-27), and all remain on study with objective stable disease. No unexpected drug-related adverse events have been observed in any patient to date. Changes in levels of MCP-1, MIP-1α, MIP- 1ß, and RANTES tracked closely for all three low dose-cohort subjects. In one subject who experienced a 46% PSA decline after 8 weeks and a 20% measurable metastatic disease reduction per RECIST 1.1 after 12 weeks of therapy, MCP-1 levels spiked 17.5-, 17.2-, 4.2- and 6.8-fold over baseline levels one week after vaccinations #1, 2, 3 and 5 respectively, and returned to within 8-30% of baseline levels the following week. In this same patient, IFNγ and GM-CSF levels followed a similar pattern; GM-CSF spiked from undetectable baseline levels to 22.0, 16.2, 9.9, and 11.7 pg/ml one week after vaccinations #1, 2, 3 and 5 respectively, and returned to undetectable levels the following week. In a second patient, who experienced a 6% PSA decline after 12 weeks of therapy, GM-CSF levels spiked from undetectable levels to 63.2 pg/mL at week 5, returning to undetectable levels over the next 7 weeks. Serum IL-6 levels for the low dose cohort fell from a mean of 9.3 pg/mL at baseline (med 5.2, range 4-18.8), to a mean of 1.6 pg/mL (med 1.2, range 1.0-2.6) at 6 weeks and a mean of 0.6 pg/mL (med 0.09, range 0-1.8) at 12 weeks.
Conclusions: In two of three subjects completing 12 weeks of therapy at the lowest dose, dramatic spikes in serum inflammatory cytokine levels correlated with PSA declines in both and measurable disease decline in one. Serum IL-6 levels, which may have prognostic value in patients with mCRPC, fell significantly (65-99%) in all three subjects. By the end of March, 2010, three patients in the mid-dose cohort (12.5 × 106 cells) will have completed 12 weeks of therapy, and enrollment of up to six patients in the high dose cohort (25 × 106 cells) will have begun.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-80.