Monocytes were purified from the leukapheresis product using a proprietary tangential-flow filtration method. Cells were placed in Teflon tissue culture bags and differentiated into immature DC for 5 days in the presence of granulocyte macrophage colony-stimulating factor. Cells were cultured for 5 days, and then killed BCG mycobacteria and IFNg were added to induce DC activation.
Three dose levels were included in this study: 2 million, 6 million, and 15 million aDCs. The first aDC injection took place approximately 3 weeks after the leukapheresis, and subsequent injections were administered at 1, 2, 8, 16, and 32 weeks after the first injection. All injections were administered to either a primary or metastatic tumor as follows. First, an 18-G guide needle was placed using image guidance [computed tomography (CT), ultra- sound, or magnetic resonance imaging (MRI)] and the commonly used coaxial technique, which provided access to the tumor. Then, a 20-G trucut core biopsy device was inserted, followed by a thinner 22-G needle to deliver the product directly into tumor tissue.
Despite the high levels of cytokines produced by the aDC, there was no evidence of cytokine- mediated toxicity. No DLTs were observed during the dose-escalation trial design, maximum tested dose (15 million aDCs) was well tolerated. Treatment-related adverse events were observed in 32 patients (82.1%), but the vast majority of these events were deemed to be grade 1 or 2 and most had resolved by the end of the study period. The most common adverse events were pyrexia (n=31; 79.5%), chills (n=16, 41.0%), fatigue (n =12, 30.8%), injection site pain or discomfort (n=11, 28.2%), night sweats (n=10, 25.6%), decreased appetite (n=9, 23.1%), and myalgia (n=7, 17.9%). There were four grade 3 (10.3%) and one grade 4 (2.6%) treatment-related serious adverse events, all at the 6 million aDCs per injection dose.
At week 8 of vaccination: 20 patients achieved stable disease (1.5 months – 48.5 months) and 14 patients had progressed disease (2.8 months – 45.1 months).
Intratumorally aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes.
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Scientific article publishing date : 7/17/2018
Immucura identifier BSC21_179EN