A recent study published in OncoImmunology by Maite Álvarez and her team at the University of Navarra explores an innovative strategy for cancer treatment. This work analyzes the use of BO-112, a compound that mimics viral RNA, in combination with immunotherapy to reduce cancer spread before surgery.
BO-112 is a nanocomplexed form of poly I:C, a compound that simulates the presence of viruses in the body. When injected directly into tumors, BO-112 activates intracellular receptors such as TLR3 (Toll-like receptor 3) and MDA5 (melanoma differentiation-associated protein 5), both involved in detecting viral RNA. This activation triggers a signaling cascade that results in the production of type I interferons and other proinflammatory cytokines. These substances recruit and activate immune cells, such as dendritic cells and CD8+ T cells, to mount a potent immune response against cancer cells.
The team used preclinical models of mice with colon and breast cancer to evaluate the effects of BO-112 in a neoadjuvant setting (prior to surgery). The mice were treated with intratumoral injections of BO-112 combined with systemic anti-PD-1 therapies. Subsequently, the primary tumors were surgically removed, and the organs affected by metastases, such as the liver and lungs, were analyzed. The study also included advanced techniques, such as flow cytometry, to examine the tumor microenvironment and evaluate the presence of CD8+ T cells (cytotoxic) and cDC1 dendritic cells, which are essential for an effective immune response.
Figure 1. Combined neoadjuvancy process (BO-112 and anti-PD-1) and its effect on tumor microenvironment and immune modulation.
The results were highly promising. The combination of BO-112 and anti-PD-1 significantly reduced the spread of cancer cells to the liver and lungs compared to individual treatments. Additionally, CD8+ T cells, responsible for attacking cancerous cells, increased in the treated tumors, and their ability to recognize tumor antigens improved markedly. On the other hand, the importance of cDC1 dendritic cells was highlighted, as they play a key role in activating CD8+ T cells. In mouse models lacking these dendritic cells, the benefits of BO-112 disappeared, underscoring their essential role in the immune response. Moreover, the mice tolerated the treatment well, with minimal adverse effects, further reinforcing the safety of this strategy.
Although these results come from preclinical studies, they provide a solid foundation for future research in humans. In particular, the combination of BO-112 with anti-PD-1 therapies could improve the efficacy of current immunotherapy, especially in patients with resistant tumors, reduce the risk of relapse after surgery by stimulating a systemic immune response against potential micrometastases, and be applied to various cancer types, such as melanoma, breast cancer, and colon cancer.
The use of BO-112 in a neoadjuvant setting represents an exciting advancement in the fight against cancer. This approach not only leverages the power of the immune system but also establishes a new strategy to reduce cancer spread before surgery. With further research, it could become an essential tool for improving survival rates and the quality of life of patients.
Main Reference:
Alvarez, M., Molina, C., Garasa, S., Ochoa, M. C., Rodriguez-Ruiz, M. E., Gomis, G., Cirella, A., Olivera, I., Glez-Vaz, J., Gonzalez-Gomariz, J., luri-Rey, C., Azpilikueta, A., Bolaños, E., Teijeira, A., Berraondo, P., Quintero, M., & Melero, I. (2023). Intratumoral neoadjuvant immunotherapy based on the BO-112 viral RNA mimetic. Oncoimmunology, 12(1). https://doi.org/10.1080/2162402x.2023.2197370
Other References:
Melero, I., Castanon, E., Alvarez, M., Champiat, S., & Marabelle, A. (2021). Intratumoural administration and tumour tissue targeting of cancer immunotherapies. Nature reviews. Clinical oncology, 18(9), 558–576. https://doi.org/10.1038/s41571-021-00507-y
Hong, W. X., Haebe, S., Lee, A. S., Westphalen, C. B., Norton, J. A., Jiang, W., & Levy, R. (2020). Intratumoral Immunotherapy for Early-stage Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 26(13), 3091–3099. https://doi.org/10.1158/1078-0432.CCR-19-3642
Chesney, J. A., Ribas, A., Long, G. V., Kirkwood, J. M., Dummer, R., Puzanov, I., Hoeller, C., Gajewski, T. F., Gutzmer, R., Rutkowski, P., Demidov, L., Arenberger, P., Shin, S. J., Ferrucci, P. F., Haydon, A., Hyngstrom, J., van Thienen, J. V., Haferkamp, S., Guilera, J. M., Rapoport, B. L., … Gogas, H. (2023). Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 41(3), 528–540. https://doi.org/10.1200/JCO.22.00343
