Monocytes from leukapheresis products were selected by CD14 immunomagnetic selection and were cultured in MACS GMP Cell Culture using GMP standard procedures for 7 days in AIM-V serum-free media supplemented with GM- CSF (1000 U/ml) and IL-4 (500 U/ml). Cytokines were replenished on day 4. DC were exposed to autologous tumor lysate generated by 5 rounds of freezing/thawing and 10 Gy irradiation with a 5 min-long heating step at 100oC during the first thawing step. DC-loading with lysate was carried out with 50-200 μg/ml of protein during 2 hours.
DC were then matured with clinical-grade tumor necrosis factor-α (TNFα; 50 ng/ml), IFNα (1,000 IU/ml) and poly I:C (20 mg/ml) for 24 hours. Freezing and thawing of matured and antigen-loaded DC was performed in aliquots of 10 7 cells. The first treatment was performed with cultured cells without previous freezing. Immediately after thawing cell viability assessed by trypan blue exclusion ranged from 60 to 90 %.
Patients are divided into 2 cohorts; cohort 1, patients treated with no stereotactic ablative radiotherapy (SABR) and cohort 2 patients treated with SABR.
The treatment is consisted of cyclophosphamide (600 mg/m2) on day –7 of each cycle; four daily intradermal DC vaccinations in alternating upper thigh regions from day 1 to 4 of each cycle; and image-guided intratumorally injection of 0.25 mg of Hiltonol in 0.5 ml of saline per dose into an accessible lesion on days 8 and 10 of each cycle.
There is no severe toxicity or severe AEs observed during and after the treatment. In all patients, 10 patients had 7 events of Grade 1 AEs, and 2 patients with grade 2 AEs.
In cohort 1, 4 patients achieved stable disease (3 with Kidney cancer and 1 Head & Neck) with the median OS of 31.5 months (6-51 months). Patient with head and neck carcinoma has the longest stable disease to 51 months and more. 3 patients had progressed disease (Mesothelioma and 2 Head & Neck) with the median OS of 7.5 months (3-12 months). 1 patient (thyroid) had mixed response with the OS of 7 months.
In cohort 2, 4 patients (Mesothelioma, Cervical, H&N, Ovarian) achieved stable disease with median OS of 9.5 months (4-15 months), 1 patient with prostate cancer had mixed response to treatment with 14 months OS. And 1 patient had progressed disease (ovarian) with OS of 4 months.
This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune- associated activity and signs of preliminary clinical efficacy.
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Scientific article publishing date 1/5/2018
Immucura identifier BSC21_064EN