PO.CL05.13 · 临床研究
一套完全整合的体外和体内工具,用于将微生物用作对抗癌症的新型治疗武器
A fully integrated set of in vitro and in vivo tools for utilization of micro-organisms as new therapeutic weapons against cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
在动态变化的肿瘤学领域,不断涌现出创新方法来应对复杂挑战。其中一个日益受到关注的有前景方向是开发病毒或细菌等微生物来摧毁癌细胞,并利用宿主免疫系统增强疗效。细胞内病毒和细菌抵抗力丧失以提高存活和增殖通路、肿瘤微环境的深刻变化导致免疫应答失活,以及通过EPR效应促进小颗粒在肿瘤中的蓄积,这些因素的结合使微生物能够大量且选择性地定植并攻击癌细胞。加之基因工程可降低其天然毒力和嗜性并增强其治疗潜力,通常通过表达趋化因子或抗原来(重新)激活免疫应答,或表达可触发T细胞衔接或其他生理改变的抗体或蛋白。溶瘤病毒或细菌单独使用或与特定佐剂及其他治疗药物联合使用,已显示可使原发性和转移性肿瘤显著缩小乃至完全缓解。在Oncodesign Services,我们拥有数百种现成的原位和皮下啮齿动物或人CDX和PDX肿瘤模型,可在同基因、异种或人源化免疫重建模型中研究微生物的活性和作用机制。病毒和细菌可在BSL2和BSL3条件下操作。凭借30年的经验和数千项已完成的研究,Oncodesign Services还具备提供支持的专业知识,可测试与其他化疗、免疫肿瘤治疗(ICI、ADC、BiTE、CAR-T细胞)或放疗的联合方案,以进一步增强微生物的活性。除了让我们能够评估微生物对肿瘤和/或免疫细胞影响的一系列连续检测方法(如免疫浸润表型分析、细胞因子/趋化因子谱分析、肿瘤负荷)之外,我们还开发了在简单或复杂样本中检测、定量、鉴定和定位活微生物的检测方法(如qPCR、质谱、生物发光)。在本海报中,我们将重点介绍在癌症背景下获得的一些结果,例如改造微生物的免疫刺激特性、对肿瘤组织的选择性感染,或在递送治疗性蛋白或抗原方面的益处。
查看英文原文 English 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 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.
利益披露 Disclosure
G. Serin, None..
L. Demontoux, None..
E. Bertrand, None..
M. Leblanc, None..
S. Maubant, None..
I. Benzaid, None..
M. Hillairet De Boisferon, None.