Tumor epitope detection in monocytes (EDIM) as a marker for antitumoral activity of Newcastle disease virus infusion and modulated electrohyperthermia

Active specific tumor vaccination with autologous dendritic cells is an emerging treatment strategy for several cancer types. Feasibility and lack of toxicity is demonstrated in numerous clinical trials. In order to improve the potency for the induction of effective tumor control, combination approaches are studied, including oncolytic virotherapy and modulated electrohyperthermia (mEHT), both inducers of immunogenic cell death (ICD). Patients (n = 24) were treated with daily infusions of Newcastle Disease Virus (NDV) and with mEHT as part of multimodal immunotherapy. Blood was followed with flow cytometry on a daily basis for change of two tumor epitopes in monocytes using the EDIM test: the DNaseX/Apo10 proteine epitope, a marker of abnormal apoptosis and proliferation, and Transketolase-like 1 (TKTL1), a marker for anaerobic glucose metabolism (Warburg effect). Patients were in median 54 years (range 3 – 79). Cancer categories were neuro-oncology (n = 11), urologic (n = 2), gynecologic (n = 5), digestive (n = 5) and pulmonary (n = 1) oncology. For all cancer types we found a significant increase in the score for Apo10, TKTL1 and the sum of both from the first till the sixth treatment. In 9 patients, we were able to follow the same variables during a second week of treatment, scheduled 3 weeks after the first. The scores were returned to the basic value, but again increased significantly upon daily NDV/mEHT treatment. The data demonstrate that NDV/mEHT target tumor cells, and induce ICD with release of Apo10 and TKTL-1, taken up by circulating monocytes and detected in EDIM test.