OncoImmunology (Dec 2023)

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

  • Maite Alvarez,
  • Carmen Molina,
  • Saray Garasa,
  • Maria C. Ochoa,
  • Maria E Rodriguez-Ruiz,
  • Gabriel Gomis,
  • Assunta Cirella,
  • Irene Olivera,
  • Javier Glez-Vaz,
  • Jose Gonzalez-Gomariz,
  • carlos luri-Rey,
  • arantza azpilikueta,
  • Elixabet Bolaños,
  • Alvaro Teijeira,
  • Pedro Berraondo,
  • Marisol Quintero,
  • Ignacio Melero

DOI
https://doi.org/10.1080/2162402X.2023.2197370
Journal volume & issue
Vol. 12, no. 1

Abstract

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ABSTRACTBO-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.

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