Radiotherapy combined with the immunocytokine (L19-IL2) provides long-lasting anti-tumor effects
Menée sur un modèle murin, cette étude montre qu'un traitement combinant une radiothérapie et l'interleukine IL2 couplée à L19, une molécule ciblant l'extra-domaine B de la fibronectine (un marqueur de la néo-angiogenèse tumorale), peut avoir des effets antitumoraux durables
Purpose : Radiotherapy (RT) modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy (IT). L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neo-angiogenesis, and can be used as immunocytokine when coupled to interleukin-2 (IL2). We hypothesize that RT in combination with L19-IL2 provides an enhanced antitumor effect, which is dependent on ED-B expression. Experimental Design : Mice were injected with syngeneic C51 colon carcinoma, Lewis lung carcinoma (LLC), or 4T1 mammary carcinoma cells. Tumor growth delay, underlying immunological parameters and treatment toxicity were evaluated after single-dose local tumor irradiation and systemic administration of L19-IL2 or equimolar controls. Results : ED-B expression was high, intermediate and low for C51, LLC and 4T1, respectively. The combination therapy showed (i) a long-lasting synergistic effect for the C51 model with 75% of tumors being cured, (ii) an additive effect for the LLC model, and (iii) no effect for the 4T1 model. The combination treatment resulted in a significantly increased cytotoxic (CD8+) T-cell population for both C51 and LLC. Depletion of CD8+ T-cells abolished the benefit of the combination therapy. Conclusion : These data provide the first evidence for an increased therapeutic potential by combining RT with L19-IL2 in ED-B positive tumors. This new opportunity in cancer treatment will be investigated in a Phase I clinical study for patients with an oligometastatic solid tumor (NCT02086721).