Killed Klebsiella pneumoniae treatment reduces tumor burden in murine melanoma

Abstract Acute infection in a cancer-bearing organ has been associated with improved prognosis and enhanced survival, although the anti-cancer immune mechanisms remained undefined. In collaboration with Qu Biologics, we hypothesized that stimulating pathogen-specific immunity, using bacteria that have previously infected specific organs, may induce protective anti-cancer immune responses in those target organs. We evaluated Klebsiella-mediated anti-cancer efficacy in metastatic-like B16 melanoma using heat-killed Klebsiella pneumoniae (Qu Biologics’ drug product QBKPN Site Specific Immunomodulator [SSI]). Subcutaneous injection of QBKPN SSI significantly reduced tumor burden. Furthermore, subcutaneous treatment with heat-killed E. coli, (QBECO SSI) reduced lung tumor burden but not as substantially as with QBKPN. This suggests that subcutaneous immune induction using a lung specific-pathogen activates a lung-specific antitumor response. We next asked whether pre-exposure to K. pneumoniae would improve anti-tumor efficacy. We exposed mice to live K. pneumoniae via intratracheal infection prior to subcutaneous injections with QBKPN SSI. Pre-exposure to K. pneumoniae significantly enhanced QBKPN SSI-induced anti-tumor immunity and control of metastatic-like B16 melanoma in the lungs. The anti-tumor efficacy in exposed mice correlated with an influx of monocytes and neutrophils, but did not correlate with an influx of T cells into the lungs. Collectively, these data suggest pre-exposure to K. pneumoniae may induce tissue resident memory cells that mediate tumor cytolysis, and thus explain the lack of T cell infiltration into the lungs.