Assessing biosimilarity of Trastuzumab monoclonal antibody therapeutics using RNA sequencing of treated SKBR3 cells

ABSTRACT: Patents of some therapeutic monoclonal antibodies (mAb) used for cancer treatment are ending soon, allowing for the entry of similar analogs (biosimilars) onto the market. To have a biosimilar approved by health agencies, the manufacturer must typically demonstrate functional and physicochemical similarity between the biosimilar and the approved reference product. Functional similarity is often validated with cell-based assays, but the information gained is limited. In contrast, RNA-seq methods enable a sensitive transcriptomic analysis, providing detailed information on pathways and cellular responses. Trastuzumab inhibits signaling of the cell-surface receptor HER2, which is overexpressed in approximately 30% of all breast cancer patients. Here, we compare the functional effect of the mAb Trastuzumab and a corresponding biosimilar. The SKBR3 breast cancer cell line was treated with the reference product, Trastuzumab (Herceptin®), or a proposed biosimilar (ApoTras), and the cellular transcriptomes were analyzed by RNA-seq. Functional similarity was assessed using two statistical contrasts. One contrast evaluated the mechanism of action by comparing treated samples (Her and ApoTras, n = 16) vs. untreated controls (n = 8). The other contrast directly compared ApoTras (n = 8) vs. Her (n = 8) to determine differences in expression between treatments. A gene set overrepresentation analysis of DEG for mAb treatments revealed mechanisms of action, which were consistent with known trastuzumab effects.

ORGANISM(S): Homo sapiens

PROVIDER: GSE284388 | GEO | 2024/12/22

REPOSITORIES: GEO