Abstract
Tumor-selective viruses are a novel therapeutic approach for treating cancer. Tumor-Specific Immuno Gene Therapy (T-SIGn) vectors are tumor-selective adenoviral vectors designed to express immunomodulatory transgenes. Prolonged activated partial thromboplastin time (aPTT), associated with the presence of antiphospholipid antibodies (aPL), has been observed in patients with viral infections, and following administration of adenovirus-based medicines. aPL may be detected as lupus anticoagulant (LA), anti-cardiolipin (aCL) and/or anti-beta 2 glycoprotein antibodies (aβ2GPI). No subtype alone is definitive for development of clinical sequalae, however, patients who are 'triple positive' have a greater thrombotic risk. Additionally, isolated aCL and aβ2GPI IgM do not appear to add value in thrombotic association to aPL positivity, rather IgG subtypes must also be present to confer an increased risk. Here we report induction of prolonged aPTT and aPL in patients from eight Phase 1 studies who were treated with adenoviral vectors (n = 204). Prolonged aPTT (≥ Grade 2) was observed in 42% of patients, with a peak at 2-3 weeks post-treatment and resolution within ~ 2 months. Among patients with aPTT prolongation, LA, but not aCL IgG nor aβ2GPI IgG, was observed. The transience of the prolongation and discordance between positive LA and negative aCL/aβ2GPI IgG assays is not typical of a prothrombotic state. Among the patients with prolonged aPTT there was no evidence of an increased rate of thrombosis. These findings elucidate the relationship between viral exposure and aPL in the context of clinical trials. They suggest a framework in which hematologic changes can be monitored in patients receiving similar treatments.Clinical trial registration:NCT02028442, NCT02636036, NCT02028117, NCT03852511, NCT04053283, NCT05165433, NCT04830592, NCT05043714.