Detalle Publicación


Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors

Autores: Marquez-Rodas, I. (Autor de correspondencia); Longo, F. ; Rodríguez Ruiz, María Esperanza; Calles, A. ; Ponce, S. ; Jove, M. ; Rubio-Viqueira, B. ; Pérez Gracia, José Luis; Gomez-Rueda, A.; Lopez-Tarruella, S.; Ponz Sarvisé, Mariano; Alvarez, R.; Soria-Rivas, A.; de Miguel, E. ; Ramos-Medina, R.; Castañón Álvarez, Eduardo; Gajate, P. ; Sempere-Ortega, C. ; Jimenez-Aguilar, E.; Aznar Gómez, María Ángela; Calvo, A. ; Lopez-Casas, P. P.; Martín Algarra, Salvador; Martin, M. ; Tersago, D.; Quintero, M.; Melero Bermejo, Ignacio
ISSN: 1946-6234
Volumen: 12
Número: 565
Fecha de publicación: 2020
Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti-programmed cell death protein-1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti-PD-1 agent might be a strategy to revert anti-PD-1 resistance.