Continuous Intra-Lymphatic Dendritic Cell Infusion in Patients with Advanced Melanoma (41.51)

Abstract

Abstract Continuous intralymphatic delivery of dendritic cells (DCs), using implantable lymphatic cannulas, allows to efficiently deliver "non-exhausted" DCs to draining lymph nodes without the disruption of nodal structures, and to recreate the physiologic kinetics of DC accumulation observed during physiologic immune responses. We have completed initial feasibility and safety evaluation of semi-continuous intralymphatic infusions of antigen-loaded DCs (a total of 300,000 DCs over 4 days) in six patients with stage IIIb-IV melanoma in clinical trial UPCI 03-118. Four of the initial six patients received two four-day-long courses of the intralymphatic DC infusions, completing the protocol. Two patients did not complete the treatment for reasons unrelated to the protocol. Already at this ultra-low dose of DCs, we have observed evidence of clinical efficacy of DC infusions in 3 of 4 patients with stage IV melanoma who completed both courses of treatment. We observed one near-complete response (currently >20 months), and two disease stabilizations (10 months; and > 7 months), with only one patient progressing. We have recently initiated the evaluation of "high-dose" intralymphatic infusions (total of 3 million DCs over 4 days). Our data demonstrate the feasibility of prolonged intralymphatic delivery of biotherapeutic agents and provide preliminary indication that DCs can be clinically effective in patients with advanced cancer at the doses 100-fold lower than previously considered to be necessary.