Oncolytic adenovirus Delta-24- RGD engineered to express 4-1BBL or OX40L as therapeutic approach for diffuse intrinsic pontine gliomas

Abstract

Pediatric tumors appear during childhood and adolescence and are diagnosed from 0 to 19 years old.1 The WHO estimates that 400,000 cases are diagnosed every year globally, which account for about 1% of all cancer diagnoses. 2 Pediatric tumors differ substantially from tumors occurring in adults. While adult cancer occurs due to the accumulation of genetic mutations and cell damage with age, pediatric tumors are usually caused by a blockage in the maturation of immature developing cell types. Therefore, the latter show much lower genetic aberrations. 3,4 The most frequently diagnosed tumors during childhood are hematological malignancies (including leukemia and lymphoma), followed by tumors of the central nervous system (CNS). Specifically, leukemia (24.7%), tumors of the central nervous system (17.2%), non-Hodgking lymphoma (7.5%), Hodgking lymphoma (6.5%), soft-tissue sarcoma (5.9%) and bone tumors (4-8%) are the most common groups5 (Figure 1). In this work, we will focus on brain tumors, and specifically on diffuse midline gliomas (DMGs).