| Description |
In this study, we will established a set of novel OVV that carrying anti-CD47 antibody gene, or anti-CD47 antibody gene combined with anti-PD-1 antibody gene, respectively. This design is based on the previous data showing that OVV and anti-CD47 antibody-mediated phagocytosis could induce immunogenic cell death and that PD-L1 is also overexpressed in some subtype of DLBCL. The insertion of anti-CD47 and anti-PD-1 antibody into the genome of an OVV shares the advantages of virotherapy and stimulation of innate immune and adoptive immunotherapy, which can not only directly kill lymphoma cells by oncolysis, but also inhibit CD47/SIRPα pathway and PD-1/PD-L1 pathway, thereby resulting in a potent activity against lymphoma. To study the mechanisms underlying anti-CD47 antibody and anti-PD-1 antibody resistance, we will analyze immunotype of immune cells and transcriptome of lymphoma cells and immune cells in tumor microenvironment by using multiparametric mass cytometry and microwell-seq, a high-throughput and low cost single-cell RNA-seq platform. Together, this study will provide a new therapeutic strategy for DLBCL and a better understanding of the mechanisms that contribute to the resistance to anti-CD47 antibody and anti-PD-1 antibody. |
