Immunocytokines in cancer treatment: A systematic review

Introduction: Immunocytokines are an emerging class of antibody-cytokine fusion proteins combining the specificity of monoclonal antibodies with the potent immunostimulatory effects of cytokines, potentially enhancing the anti-tumor immune response while reducing systemic toxicity. Methods: We conducted a systematic review following the PRISMA guidelines. We performed a comprehensive literature search using PubMed and ClinicalTrials.gov databases. The search strategy included the terms “immunocytokine”, “cytokine”, “tumor”, and “cancer”. Filters were applied to retrieve only peer-reviewed articles and clinical trials. Results: 25 publications were retrieved: 15 were Phase I studies; 2 Phase I/II, and 8 Phase II. Regarding ongoing clinical trials, 62 studies were included: 30 were Phase I studies, 2 Phase III, and the remaining 30 were either Phase II (n = 13) or Phase I/II (n = 17). In 50/62 trials, the primary and co-primary outcomes included safety measures, such as adverse effects, dose-limiting toxicities, and maximum tolerated dose. In both studies from literature and ongoing clinical trials, the most common target was extra-domain B (EDB) of fibronectin, and the most investigated type of cancer was melanoma. While all published studies focused on solid tumors, several ongoing trials include hematologic malignancies. Conclusions: Research interest in immunocytokines as a potential cancer treatment is increasing, although only limited data are currently available. Several trials, mainly in the early phase, are ongoing, paving the way for a possible broader clinical application of this class of immunotherapeutics.