| Autor: |
Dominique Tersago, Enrique de Miguel, Mariano Ponz-Sarvise, Rocío Ramos-Medina, Marisol Quintero, Ainara Soria-Rivas, Ana Gómez-Rueda, Aitana Calvo, Santiago Ponce, Maria E. Rodriguez-Ruiz, Antonio Calles, Ignacio Melero, Sara López-Tarruella, Ivan Marquez-Rodas, M. Angela Aznar, Salvador Martín-Algarra, Jose Luis Perez-Gracia, Federico Longo, Belen Rubio-Viqueira, Elisabeth Jiménez-Aguilar, Pablo Gajate, Rosa Alvarez, Eduardo Castanon, Maria Jove, Cayetano Sempere-Ortega, Pedro P. López-Casas, Miguel Martín |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Science translational medicine. 12(565) |
| ISSN: |
1946-6242 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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