Combined Immunotherapy encompassing intratumorally poly-ICLC, Dendritic Cell Vaccination and Radiotherapy in Advanced Cancer Patients

Irradiated lessions

Irradiated lessions

CONTACT US

Summary

This study aims to evaluate the efficacy of radio-immunotherapy combination strategy on patients with advanced cancer. This radio-immunotherapy combination strategy, targetted at resembling viral infection in tumor tissue combined with a Dendritic-Cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.

Patients characteristics

17 patients ages 40-70 years old with treatment-refractory histologically confirmed solid tumors. Eligible patients had metastatic disease that had progressed on a standard therapy and at least one tumor lesion suitable for Hiltonol injection (and radiotherapy administration in the case of cohort 2 patients). All patients had ECOG (Eastern Cooperative Oncology Group) performance status of 0-1 and adequate hematological, liver and renal function.

Methodology

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 %.

Treatment

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.

Results

Adverse reaction
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.
Clinical outcomes
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.

Conclusion

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.

Article Reference link: click here

Scientific article publishing date 1/5/2018

Immucura identifier BSC21_064EN

ALL SCIENTIFIC PAPERS
CONTACT US