Establishment Of Breast Cancer PDX Model And Screening Of Antibody Drugs

Breast cancer is currently one of the most common malignant tumors worldwide and is a major cause of cancer-related deaths in women.However,the pathogenesis of breast cancer remains to be elucidated.There are many subtypes in breast cancer with different genetic,pathological and clinical manifestations,which makes it more difficult for clinical diagnosis and treatment of breast cancer.Patient-derived tumor xenograft(PDX)model is established by directly transplanting human tumor specimens into animals with severe immunodeficiency,which is a commonly used tool for evaluating the efficacy of different tumor treatment in vivo.The advantage of the PDX model is that it retains tumor heterogeneity and provides the opportunity for developing personalized treatment.In this study,a total of 49 fresh breast cancer clinical samples were collected from hospitals,and were injected subcutaneously into severe immunodeficiency mice(NCG)to establish breast cancer PDX models.So far,20 breast cancer PDX models have been successfully established,with an overall success rate of 40.8%.By analyzing the correlation between clinical factors and tumor formation rate,it was found that samples from triple-negative breast cancer had a significantly higher tumor formation rate than the non-triple-negative breast cancer samples(P=0.0140).Similarly,the CK5/6 positive samples showed significantly higher tumor formation rate than CK5/6 negative samples(P=0.0144).Single breast cancer cells were isolated from the PDX mouse model successfully established in this study.Anti-ROR2 antibodies that inhibited tumor cell invasion were screened by in vitro invasion experiments.The half-life of the antibody was 50 hours as detected by pharmacokinetic experiments.Finally,through in vivo antitumor experiments in PDX mice,we found that the antibody can effectively inhibit tumor growth in breast cancer PDX models.