Predictive and Prognostic Clinical Variables in Cancer Patients Treated With Adenoviral Oncolytic Immunotherapy

Abstract

The development of oncolytic viruses has recently made great progress towards being available to cancer patients. With the breakthrough into clinics, it is crucial to analyze the existing clinical experience and use it as a basis for treatment improvements. Here, we report clinical data from 290 patients treated with oncolytic adenovirus. Using clinical variables and treatment characteristics, we constructed statistical models with regard to treatment response and overall survival (OS). Additionally, we investigated effects of neutralizing antibodies, tumor burden, and peripheral blood leucocyte counts on these outcomes. We found the absence of liver metastases to correlate with an improved rate of disease control (P = 0.021). In multivariate evaluation, patients treated with viruses coding for immunostimulatory granulocyte macrophage colony-stimulating factor were linked to better prognosis (hazard ratio (HR) 0.378, P < 0.001), as well as women with any cancer type (HR 0.694, P = 0.017). In multivariate analysis for imaging response, patients treated via intraperitoneal injection were more likely to achieve disease control (odds ratio (OR) 3.246, P = 0.027). Patients with low neutrophil-to-lymphocyte ratio before treatment had significantly longer OS (P < 0.001). These findings could explain some of the variation seen in treatment outcomes after virotherapy. Furthermore, the results offer hypotheses for treatment optimization and patient selection in oncolytic adenovirus immunotherapy.

Adenovirotherapy Delivering Cytokine and Checkpoint Inhibitor Augments CAR T Cells against Metastatic Head and Neck Cancer

“…First we tested the antitumor efficacy of Onc.Ad5/3D24 because this oncolytic virus has been clinically tested in patients with solid tumors, including HNSCC. 23 We injected the virus locally into both FaDu and SCC-47 xenograft models and found that it had minimal anti-tumor effects ( Figure S5), suggesting that, like CAR T cells, oncolysis alone is insufficient to cure bulky HNSCCs. Next we confirmed that co-infection of Onc.Ad with HDAdIL12_PDL1 (CAd12_PDL1; Onc.Ad:HDAd = 1:10 4 ) amplified IL-12p70 and PD-L1-blocking antibody expression in co-infected FaDu and SCC-47 cells in vitro ( Figure 4B).…”

Interleukin 8 activity influences the efficacy of adenoviral oncolytic immunotherapy in cancer patients

“…We have previously found that neutrophil-to-lymphocyte ratio (NLR) significantly predicts survival in patients treated with oncolytic adenovirus [ 6 ]. In order to verify that IL-8 is not merely reflecting the neutrophil/lymphocyte balance in these patients, we combined baseline IL-8 and neutrophil-to-lymphocyte ratio status in a survival analysis (Figure 4C ).…”

“…The association of high IL-8 and high neutrophils is logical, since neutrophil recruitment and activation is one of the main functions of IL-8 [ 44 ]. We have previously found that neutrophil-to-lymphocyte ratio predicts survival in adenovirus treated cancer patients [ 6 ]. Therefore, it was interesting that IL-8 status was able to improve its predictive ability significantly.…”

“…Tumor load was assessed from pre-treatment CT and PET-CT images. Based on the metastases in different organs and size of the primary tumor a tumor load score (0-21) describing the overall tumor load was calculated according to previously described methodology [ 6 ]. In this study tumor load score was available for 60 patients.…”

“…After years of development, the first oncolytic viruses are currently entering the clinics as cancer therapeutics with products approved in both the East and West [ 1 – 3 ]. Despite recent discoveries relating to the mechanisms of action and factors that influence the efficacy of oncolytic viruses [ 4 – 6 ], there is still a critical need to identify pathways that determine the response to virotherapy and survival benefits thereafter. In this regard, analysis of patient data is of key importance since immunological effects of human-specific agents may significantly differ between humans and experimental animals.…”