Molina, C. (Carmen)

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    Intratumoral neoadjuvant immunotherapy based on the BO-112 viral RNA mimetic
    (2023) Glez-Vaz, J. (Javier); Berraondo, P. (Pedro); Cirella, A. (Assunta); Azpilikueta, A. (Arantza); González-Gomariz, J. (José); Bolaños, E. (Elixabet); Rodriguez-Ruiz, M.E. (María Esperanza); Garasa, S. (Saray); Gomis, G. (Gabriel); Quintero, M. (Marisol); Molina, C. (Carmen); Ochoa, M.C. (María Carmen); Melero, I. (Ignacio); Álvarez, M. (Maite); Olivera, I. (Irene); Luri-Rey, C. (Carlos); Teijeira, A. (Álvaro)
    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.