Strauss Bryan E, Silva Gissele Rolemberg Oliveira, de Luna Vieira Igor, Cerqueira Otto Luiz Dutra, Del Valle Paulo Roberto, Medrano Ruan Felipe Vieira, Mendonça Samir Andrade
Laboratório de Vetores Virais, Centro de Investigação Translacional em Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Clinics (Sao Paulo). 2018 Sep 6;73(suppl 1):e479s. doi: 10.6061/clinics/2018/e479s.
While cancer immunotherapy has gained much deserved attention in recent years, many areas regarding the optimization of such modalities remain unexplored, including the development of novel approaches and the strategic combination of therapies that target multiple aspects of the cancer-immunity cycle. Our own work involves the use of gene transfer technology to promote cell death and immune stimulation. Such immunogenic cell death, mediated by the combined transfer of the alternate reading frame (p14ARF in humans and p19Arf in mice) and the interferon-β cDNA in our case, was shown to promote an antitumor immune response in mouse models of melanoma and lung carcinoma. With these encouraging results, we are now setting out on the road toward translational and preclinical development of our novel immunotherapeutic approach. Here, we outline the perspectives and challenges that we face, including the use of human tumor and immune cells to verify the response seen in mouse models and the incorporation of clinically relevant models, such as patient-derived xenografts and spontaneous tumors in animals. In addition, we seek to combine our immunotherapeutic approach with other treatments, such as chemotherapy or checkpoint blockade, with the goal of reducing dosage and increasing efficacy. The success of any translational research requires the cooperation of a multidisciplinary team of professionals involved in laboratory and clinical research, a relationship that is fostered at the Cancer Institute of Sao Paulo.
尽管癌症免疫疗法近年来备受关注，但在优化这些疗法的许多方面仍未得到探索，包括开发新方法以及针对癌症免疫循环多个环节的治疗策略性组合。我们自己的工作涉及利用基因转移技术促进细胞死亡和免疫刺激。在我们的研究中，由交替阅读框（人类中的p14ARF和小鼠中的p19Arf）与干扰素-β cDNA联合转移介导的这种免疫原性细胞死亡，在黑色素瘤和肺癌小鼠模型中显示出可促进抗肿瘤免疫反应。基于这些令人鼓舞的结果，我们现在正朝着新型免疫治疗方法的转化和临床前开发迈进。在此，我们概述了我们面临的前景和挑战，包括使用人类肿瘤和免疫细胞来验证在小鼠模型中观察到的反应，以及纳入临床相关模型，如患者来源的异种移植瘤和动物自发性肿瘤。此外，我们试图将我们的免疫治疗方法与其他治疗方法，如化疗或检查点阻断相结合，以达到减少剂量和提高疗效的目的。任何转化研究的成功都需要参与实验室和临床研究的多学科专业团队的合作，这种合作关系在圣保罗癌症研究所得到了促进。
