Introduction: Bacillus Calmette-Guérin (BCG) is a live attenuated mycobacterium vaccine. Since more than four decades ago, intravesical BCG represents a gold standard therapy for high-risk non-muscular invasive bladder cancer. Recently, systemic delivery of BCG has recently been reported to drive profound changes in bone marrow myelopoiesis providing a more efficient capacity of response against a subsequent tuberculosis infection. However, intravenous (i.v.) BCG has never been studied in the context of orthotopic lung tumors.

Objective: The aim of this project is to study the antitumoral response of i.v. BCG in a metastatic lung adenocarcinoma mouse model.

Methods: A metastatic lung adenocarcinoma mouse model was developed inoculating intravenously (i.v.) lung cancer cells from mice-bearing KrasG12V mutation. To study the efficacy of i.v. BCG, mice were vaccinated i.v. with 106 CFU of BCG.

Results: Mice inoculated with i.v. BCG prior to tumor cells inoculation showed higher survival compared to non-treated mice. However, i.v. BCG delivery after tumor challenge did not provide any therapeutic advantage, suggesting that tumor might be influencing i.v. BCG efficacy. Moreover, prior administration of i.v. BCG avoided myeloid-derived supressor cells (MDSCs) accumulation in lungs of tumor-bearing mice, in contrast to i.v. BCG after tumor challenge leading to an immunosuppresive ambience. Finally, therapeutic combination of i.v. BCG with gemcitabine, which reduce MDSCs at low doses, futher increased mouse survival compared to gemcitabine in monotherapy.

Conclusion: As a result, combination of i.v. BCG with chemotherapy could represent an attractive therapeutic approach for advanced lung cancer.