Intratumoral neoadjuvant immunotherapy based on the BO-112 viral RNA mimetic

05-abr-2023 | Revista: Oncoimmunology

Maite Alvarez 1 2 3 , Carmen Molina 1 2 , Saray Garasa 1 2 , Maria C Ochoa 1 2 3 , Maria E Rodriguez-Ruiz 4 , Gabriel Gomis 1 2 , Assunta Cirella 1 2 , Irene Olivera 1 2 , Javier Glez-Vaz 1 2 , Jose Gonzalez-Gomariz 1 2 , Carlos Luri-Rey 1 2 , Arantza Azpilikueta 1 2 , Elixabet Bolaños 1 2 , Alvaro Teijeira 1 2 3 , Pedro Berraondo 1 2 3 , Marisol Quintero 5 , Ignacio Melero 1 2 3 4 6

Abstract

BO-112 is a poly I:C-based viral mimetic that exerts anti-tumor efficacy when intratumorally delivered in mouse models. Intratumoral BO-112 synergizes in mice with systemic anti-PD-1 mAbs and this combination has attained efficacy in PD1-refractory melanoma patients.

We sought to evaluate the anti-tumor efficacy of BO-112 pre-surgically applied in neoadjuvant settings to mouse models. We have observed that repeated intratumoral injections of BO-112 prior to surgical excision of the primary tumor significantly reduced tumor metastasis from orthotopically implanted 4T1-derived tumors and subcutaneous MC38-derived tumors in mice. Such effects were enhanced when combined with systemic anti-PD-1 mAb.

The anti-tumor efficacy of this neoadjuvant immunotherapy approach depended on the presence of antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells. Since BO-112 has been successful in phase-two clinical trials for metastatic melanoma, these results provide a strong rationale for translating this pre-surgical strategy into clinical settings, especially in combination with standard-of-care checkpoint inhibitors.

CITA DEL ARTÍCULO Oncoimmunology. 2023 Apr 5;12(1):2197370. doi: 10.1080/2162402X.2023.2197370. eCollection 2023.

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