GÉTICA 2021

41 [ F I T C á n c e r - 7 ] and BAFT3 genes were used to delineate the im- mune system requirements for efficacy. Results: In cultures of TSA breast cancer cells the combination of irradiation and BO-112 showed more prominent features of immunogenic tu- mor-cell death including type I interferon release. Injection of BO-112 in the tumor lesions under radiation achieved excellent control of the treat- ed tumors whilst modest delays in contra lateral tumor progression were observed. Local effects were associated with more prominent presence of antitumor CTLs and cDC1 dendritic cells in the tumor and regional lymph nodes. Importantly, lo- cal irradiation plus BO-112 in a tumor lesion en- hanced the therapeutic effect of radiotherapy on distant uninjected tumor lesion. Conclusions: This study demonstrates that lo- cal BO-112 immunotherapy and external beam radiation therapy can exert synergies to achieve local tumor control. This beneficial effect can be extended to non-injected lesions as long as they are also irradiated, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and at least one of them acces- sible for BO-112 repeated intratumoral injections. María Esperanza Rodríguez Ruiz Universidad de Navarra. Pamplona Background: Radioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemi- cally, but strategies for delivering immunothera- py locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy by injecting various patterns of molecules shows efficacy both preclinical and clinically. BO-112 is a viral mimetic based on nanoplexed double stranded RNA (poly IC) which exerts immune-me- diated antitumor effects in mice and humans upon intratumoral delivery. BO-112 and external beam irradiation were used to make the proof-of- concept local immunotherapy plus radiation ther- apy combinations. Methods: Murine transplantable tumor cells lines (TSA, MC38 and B16 ova) were used to show in- creased immunogenic features under irradiation as well as bilateral tumor models in which only one of the lesions could be irradiated. Flow cy- tometry on cell suspensions from tumor-draining lymph nodes and multiplex tissue immunofluo- rescence were used to determine mechanims of antitumor immunity. Depletions of of immune cell populations and knock-out mice for IFNAAR Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T cell-mediated local tumor control