A fully integrated set of in vitro and in vivo tools for utilization of micro-organisms as new therapeutic weapons against cancer.
Authors
Guillaume Serin, Lucie Demontoux, Elizabeth Bertrand, Marie Leblanc, Sylvie Maubant, Aurelie Durgeau, Isma Benzaïd, Peggy Provent, Pascal Grondin, Marc Hillairet de Boisferon
Oncodesign Services – 20 rue Jean Mazen, 21000, Dijon, France
Abstract
In the dynamic landscape of oncology, innovative approaches are constantly emerging to tackle complex challenges. One such promising avenue gaining attention is the development of micro-organisms like viruses or bacteria to destroy cancer cells and leverage the host immune system to enhance the effect.
The combination of loss of intracellular viral and bacterial resistance to increase survival and proliferation pathways, profound changes of tumor microenvironment leading to inactivation of immune response and favored tumor accumulation of small particles by EPR enables microorganisms to massively and selectively colonize and attack the cancer cells. Genetic engineering is added to reduce their natural virulence and tropism and enhancing their therapeutic potential, often by expression of chemokine or antigens to (re)activate the immune response or expression of antibodies or proteins that can trigger T cell engagement or other physiological modification. Alone or combined with specific adjuvants and other therapeutic agents, oncolytic viruses or bacteria have shown significant reduction to even full remission of primary and metastatic tumors.
At Oncodesign Services, we have hundreds of orthotopic and subcutaneous rodent or human CDX and PDX tumor models readily available to study the activity and mechanism of action of micro-organisms in syngeneic, xenogeneic or humanized immune reconstituted models. Viruses and bacteria can be manipulated in BSL2 and BSL3 status. With 30 years of experience and thousands of studies performed, Oncodesign Services has also the know-how to provide support for testing combinations with other chemo, immuno-onco (ICI, ADC, BiTEs, CAR-T cells) or irradiation therapy to further increase the activity of micro-organisms.
In addition to continuum of assays allowing us to evaluate the impact of microorganisms on tumor and/or immune cells (e.g. phenotyping of immune infiltrate, cytokine/chemokine profiling, tumor burden), we have developed assays to detect, quantify, identify and localize live microorganisms (e.g. qPCR, mass spectrometry, bioluminescence) in simple or complex samples.
In this poster, we will highlight some results obtained in a cancer context such as the immunostimulatory properties of modified micro-organisms, the selective infection of tumor tissue or the benefits in delivery of therapeutic proteins or antigens.
