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

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.

KEYWORDS:

• BO-112
• intratumoral immunotherapy
• metastases
• neoadjuvant
• PD-1

Acknowledgments

We would like to acknowledge both CIMA/University of Navarra shared flow cytometry (Diego Alignani), image platform and animal facilities (Eneko Elizalde and Elena Ciordia) for their technical support. Professional English editing by Dr. Paul Miller is also acknowledged. Finally, we wish to thank all the members of Dr. Melero’s and Dr. Berraondo’s groups for the continuous support and helpful discussions.

Disclosure statement

CM, SG, MER, GG, AC, IO, JG, JG, CL AA, EB, AT, PB declare no competing interests. MA declares receiving a commercial research grant from Highlight Therapeutics. MCO reports receiving a commercial research grant from AstraZeneca. MQ is full-time employee of Highlight Therapeutics. IM reports receiving commercial research grants from AstraZeneca, BMS, Highlight Therapeutics, Alligator, Pfizer Genmab and Roche; has received speakers bureau honoraria from MSD; and is a consultant or advisory board member for BMS, Roche, AstraZeneca, Genmab, Pharmamar, F-Star, Bridget Peak, BioNtech, Bioncotech, Bayer, Numab, Pieris, Gossamer, Alligator and Merck Serono. IM has received consultancy fees from Highlight therapeutics.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2197370.

Additional information

Funding

This work was supported by the PID2020-112892RB-100 funded by MCIN/AEI/10.13039/501100011033, PDC2021-121769-C21 grant funded by MCIN/AEI/10.13039/501100011033 and The European Union Next GenerationEU/PRTR, Instituto de Salud Carlos III (PI22/00147) co-financed by Fondos Feder, the Fundación La Caixa (HR21-0083), the AACR-AstraZeneca career development award for physician-scientist in honor of Jose Baselga and the Fundació La Marató TV3 (488/C/2019). MA was supported by a Spanish Association Against Cancer’s Investigator grant (INVES19041ALVA) and currently receives “Ayudas Ramon y Cajal” (RYC2021-033381) from the MCIN/AEI/10.13039/501100011033.