No abstract

Oncolytic adenoviral immunotherapy activates the innate immune system with subsequent induction of adaptive tumor‐specific immune responses to fight cancer. Hence, oncolytic viruses do not only eradicate cancer cells by direct lysis, but also generate antitumor immune response, allowing for long‐lasting cancer control and tumor reduction. Their therapeutic effect can be further enhanced by arming the oncolytic adenovirus with costimulatory transgenes and/or coadministration with other antitumor therapies. ONCOS‐102 has already been found to be well tolerated and efficacious against some types of treatment‐refractory tumors, including mesothelin‐positive ovarian cancer (NCT01598129). It induced local and systemic CD8+ T‐cell immunity and upregulated programmed death ligand 1. These results strongly advocate the use of ONCOS‐102 in combination with other therapeutic strategies in advanced and refractory tumors, especially those expressing the mesothelin antigen. The in vivo work presented herein describes the ability of the oncolytic adenovirus ONCOS‐102 to induce mesothelin‐specific T‐cells after the administration of the virus in bagg albino (BALB/c) mice with mesothelin‐positive tumors. We also demonstrate the effectiveness of the interferon‐γ the enzyme‐linked immunospot (ELISPOT) assay to detect the induction of T‐cells recognizing mesothelin, hexon, and E1A antigens in ONCOS‐102‐treated mesothelioma‐bearing BALB/c mice. Thus, the ELISPOT assay could be useful to monitor the progress of therapy with ONCOS‐102.

Background TG01 is the first cancer immunotherapy targeting KRAS oncogenic mutations. This study assessed the safety and efficacy of TG01/GM-CSF in patients with resected pancreatic adenocarcinoma. Methods Patients with stage I or II pancreatic adenocarcinoma who had undergone surgical resection (R0 or R1) received adjuvant gemcitabine with TG01/GM-CSF using two schedules of vaccination. Immune response was defined as a positive delayed-type hypersensitivity (DTH) response and/or positive T-cell proliferation assay. Results Thirty-two patients were enrolled between February 2013 and May 2016. Nineteen were treated with the high antigen burden, with four serious adverse reactions considered possibly related to TG01 treatment, including three allergic reactions. On this basis, a further 13 patients received a modified vaccination schedule with reduced antigen burden, with no serious adverse events related to TG01. Ninety-five percent patients in the main cohort and 92% in the modified cohort had a positive immune response. Median overall survival (OS) was 33.1 months, and median disease-free survival (DFS) was 13.9 months for the main cohort. For the modified cohort, the median OS was 34.3 months and median DFS was 19.5 months. Conclusions TG01/GM-CSF with gemcitabine was well tolerated, with high levels of immune activation. OS and DFS compare favourably with published data for adjuvant gemcitabine. Clinical trial registration This clinical trial was registered at ClinicalTrials.gov (NCT02261714).