Site-Specific Immunomodulators (SSIs) are novel immunotherapies for cancer

Abstract

Abstract The immune system recognizes and eliminates malignant cells, and maintains an intricate balance between immune activation and cancer. Historically, spontaneous tumor regression has been observed in some patients experiencing acute microbial infections. Building upon this, it was discovered that repeated subcutaneous injection of novel immunotherapies called Site-Specific Immunomodulators (SSIs), derived from killed bacteria known to cause infection in a particular organ or tissue, may be effective at treating cancer growing in the same site. We hypothesize that SSIs stimulate the body’s immune system to reverse immune suppression and dysfunction in the tumor microenvironment, enabling effective anti-cancer immune responses. To test this hypothesis, we evaluated the efficacy of a lung-specific SSI, QBKPN, in preclinical lung cancer models. Repeated subcutaneous administration of QBKPN significantly reduced lung tumor burden at day 16 post-inoculation (p<0.0001) in the Lewis Lung Carcinoma model, improving median survival by 10 days (p<0.005). Similar results were obtained using the aggressive and poorly-immunogenic B16 lung cancer model. Anticancer efficacy was associated with site-specific infiltration of newly recruited monocytes and neutrophils to the lung and mobilization of antigen presenting cells in the lung-draining lymph node. These data complement the positive results from our compassionate use clinical data, and provide strong evidence that SSIs may improve therapeutic outcomes for cancer patients. QBKPN is currently studied in a Phase 2a clinical trial of non-small cell lung cancer in collaboration with the BC Cancer Agency (Trial NCT02256852).