This study investigates the correlation of cytokines produced by Dendritic Cells with clinical outcomes in patients with diverse cancers. The results reveal, 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.
40 patients 18–75 years of age with locally advanced or metastatic disease and who had undergone at least one antitumor treatment regimen within 12 weeks of screening were eligible for the study. Other eligibility criteria included having an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, having at least one injectable tumor mass >1 cm in diameter and located away from major vascular structures or areas not amenable to swelling (e.g., upper airway tumors), producing a sufficient number of monocytes to manufacture the full dose course, having a life expectancy >6 months, and having adequate bone marrow and renal function.
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.