An anti-cadherin (CDH)19/cluster of differentiation (CD)3 half-life extension (HLE) bispecific T cell engager (BiTE®) and AMG 757 may be effective for treating metastatic melanoma that is relapsed and/or refractory to targeted therapy and/or immune checkpoint blockade, a new study found. The findings from this study were presented at the American Association for Cancer Research 2019 Annual Meeting, held March 29 to April 3 in Atlanta, Georgia.
“The treatment landscape for metastatic melanoma has changed considerably over the last several years with the approval of targeted therapy such as BRAF inhibitors and immunotherapy such as immune checkpoint inhibitors that block cytotoxic T lymphocyte associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1),” the researchers wrote, “however, approximately 40% of patients do not respond to the current standard of care, and up to one-third of patients who initially respond to therapy can relapse. Novel therapies that act by a distinct mechanism of action may be needed to increase durable response rates in metastatic melanoma.”
Researchers produced a BiTE® antibody that features an HLE targeting CDH19 on melanoma cells and CD3 on T cells (ie, anti-CDH19/CD3 HLE BiTE®). An HLE BiTE® targeting delta-like ligand 3 (DLL3) and CD3 on T cells, anti-DLL3/CD3 HLE BiTE®, or AMG 757, was also produced.
The investigators used low cytometry to identify cell surface expression of CDH19 and DLL3 and then followed with T cell-dependent cytotoxicity assays to evaluate anti-CDH19/CD3 HLE BiTE® and AMG 757 activity against treatment-resistant melanoma cell lines. Approximately 93% of the cell lines demonstrated expression of CDH19 on the cell surface. In addition, ≤64% of the cell lines showed DLL3 expression on the cell surface. Both the HLE BiTE® and AMG 757 possessed cell-killing abilities of CDH19-positive and DLL3-positive melanoma cells, respectively.
Bailis JM, Lee F, Gi M, et al. Melanoma subtypes that emerge during adaptive resistance to therapy are targets for bispecific T cell engager (BiTE®) antibody constructs directed to CDH19 and DLL3. Poster presented at: American Association for Cancer Research Annual Meeting; March 29 to April 3, 2019; Atlanta, Georgia.