PO.CL05.03 · 临床研究

植物病毒免疫调节剂与IL-12联合治疗小鼠卵巢癌的协同疗效

Synergistic therapy by combination of a plant virus immunomodulator and IL-12 against murine ovarian cancer

海报缩略图:植物病毒免疫调节剂与IL-12联合治疗小鼠卵巢癌的协同疗效
编号 3801 展板 16 时间 4/20 02:00–05:00 区域 Section 43 主讲 Xinyi Deng, BS
分会场 Combination Immunotherapies
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作者与单位 Authors & Affiliations

Xinyi Deng1, Jessica Fernanda Affonso de Oliveira2, Nicole F. Steinmetz1

1UC San Diego, La Jolla, CA,2University of California San Diego - UCSD, San Diego, CA

摘要 Abstract

中文摘要
豇豆花叶病毒(CPMV)是一种免疫刺激剂,经瘤内治疗可通过逆转免疫抑制性肿瘤微环境(TME)诱导抗肿瘤免疫。原位注射CPMV可激活并募集固有免疫细胞,从而启动肿瘤细胞杀伤和抗原加工,最终引发全身性适应性抗肿瘤免疫。IL-12是一种前景广阔的促炎细胞因子,可促进抗原加工并推动T细胞增殖。CPMV主要激活固有免疫细胞,而IL-12在适应性免疫应答中发挥关键作用;因此,我们假设CPMV与IL-12的协同联合将有利于减轻肿瘤负荷。我们采用小鼠卵巢癌模型进行研究。给小鼠接种生物发光肿瘤细胞。通过生物发光、体重和周长监测肿瘤负荷。根据人道终点确定生存情况。我们的数据显示,CPMV+IL-12联合治疗优于单臂治疗。联合治疗组显示出强劲的疗效。在正在进行的研究中,我们正通过免疫学研究解析其作用机制。本研究部分由NIH资助:R01 CA224505和R01 CA274640。
查看英文原文 English abstract
Cowpea Mosaic Virus (CPMV) is an immunostimulatory agent that can induce antitumor immunity by reversing the immunosuppressive tumor microenvironment (TME) upon intratumoral treatment. In situ injection of CPMV activates and recruits innate immune cells which initiate tumor cell killing and antigen processing, ultimately launching systemic and adaptive antitumoral immunity. IL-12 is a promising proinflammatory cytokine that facilitates antigen processing and promotes T cell proliferation. CPMV primarily activates innate immune cells while IL-12 plays a key role in the adaptive immune response; therefore, we hypothesized that the synergistic combination of CPMV and IL-12 would be beneficial for reducing tumor burden. We tested our study using a murine ovarian carcinoma model. Mice were inoculated with bioluminescent tumor cells. Tumor burden was monitored using bioluminescence, body weight, and circumference. Survival was established based on humane endpoints. Our data show that the combination of CPMV + IL-12 outperforms the single-arm treatment. Robust efficacy is demonstrated for the combination group. In ongoing studies, we are deciphering the mechanism of action through immunological investigation. This work was funded in part through grants from NIH: R01 CA224505 and R01 CA274640.
利益披露 Disclosure
X. Deng, None.. J. F. Affonso de Oliveira, None. N. F. Steinmetz, PlantiosX Inc Other, Co-founder and CEO. Mosaic ImmunoEngineering Inc. Co-founder. Pokometz Scientific LLC Other, co-founder and manager. Ring Therapeutics, Inc Other, Paid consultant.

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