Bacterial ghosts as adjuvant to oxaliplatin chemotherapy in colorectal carcinomatosis

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality worldwide. At late stage of the disease CRC often shows (multiple) metastatic lesions in the peritoneal cavity which cannot be efficiently targeted by systemic chemotherapy. This is one major factor contributing to poor prognosis. Oxaliplatin is one of the most commonly used systemic treatment options for advanced CRC. However, drug resistanceoften due to insufficient drug deliveryis still hampering successful treatment. The anticancer activity of oxaliplatin includes besides DNA damage also a strong immunogenic component. Consequently, the aim of this study was to investigate the effect of bacterial ghosts (BGs) as adjuvant immunostimulant on oxaliplatin efficacy. BGs are empty envelopes of gramnegative bacteria with a distinct immune-stimulatory potential. Indeed, we were able to show that the combination of BGs with oxaliplatin treatment had strong synergistic anticancer activity against the CT26 allograft, resulting in prolonged survival and even a complete remission in this murine model of CRC carcinomatosis. This synergistic effect was based on an enhanced induction of immunogenic cell death and activation of an efficient T-cell response leading to long-term anti-tumor memory effects. Taken together, co-application of BGs strengthens the immunogenic component of the oxaliplatin anticancer response and thus represents a promising natural immune-adjuvant to chemotherapy in advanced CRC.

Prodigiosin-Functionalized Probiotic Ghosts as a Bioinspired Combination Against Colorectal Cancer Cells

“…Such outstanding surface features endow BGs with the ability to stimulate immune responses and serve as vectors for the delivery of human and veterinary vaccines [18][19][20]. Equally important, BGs exert therapeutic potential on their own and may synergize the activity of other drugs via BGinduced immunostimulatory effects [21]. Compared with biomaterial-based drug carriers, PGs are safer and more stable in the biological milieu and are characterized by a large internal space and inherent drug biotargeting ability [11,22].…”