Switchable bispecific antibodies for cancer-specific delivery of PEGylated nanomedicine to treat antigen-loss relapse in B cell malignancies
Targeted therapies for B
malignancies such as CD19 targeted antibody-drug conjugates and CD19-targeted
bi-specific T-cell engagers (BiTEs) therapy showed impressive results in
clinical trials. However, single-antigen targeting is associated with the risk
of relapse, with up to 30% of relapses after CD19-mediated BiTE therapy found
to be CD19-negative population. This might be due to antigen-loss mutations and
tumor heterogeneity. We hypothesize that
subsequently targeting multiple antigens (e.g. CD19, CD22, and CD52) will
improve therapy outcomes of B malignancies and control disease progression
during CD19-negative relapse. In this study, we propose to develop a switchable
bispecific antibody platform for redirecting PEGylated nanomedicines to B
malignancies to overcome antigen-loss relapse.
Development of bispecific antibodies for delivery of nanomedicines across the Blood-Brain Barrier
Approximately 10-20% of patients with non-small cell lung cancers (NSCLC) developed brain metastasis. Treatments of brain cancers typically require efficient drug delivery across the blood-brain-barrier (BBB) which is the main bottleneck for the delivery of therapeutics into the brain. Transferrin receptor (TfR) mediated transcytosis has potential use for transportation of therapeutics across the BBB, however it usually showed poor BBB penetration due to the inefficient release of the payload during transcytosis. We propose a novel approach to boost the brain uptake of nanoparticles by facilitating efficient nanoparticles release in brain endothelial cells.