New Photoimmunotherapy Approach Targets T Cells and Tumor Antigens
Key Takeaways
- An activatable photoimmunotherapy (PIT) platform designed to remain quenched until enzymatic activation occurs within target cells (Vertamax) was associated with depletion of pathogenic cells, new research suggests.
- In preclinical experiments, CD5-directed vertamax-PIT depleted T cells in healthy human skin biopsies and pathogenic T cells in a single cutaneous T-cell lymphoma (CTCL) biopsy.
- EGFR-targeted vertamax-PIT inhibited tumor growth in vivo without detectable off-target toxicity.
A new activatable photoimmunotherapy platform may enable more selective depletion of pathogenic cells while limiting inflammatory effects associated with existing PIT approaches, according to new research.
Photoimmunotherapy combines antibody-mediated targeting with light-activated cytotoxicity, allowing cell depletion to be controlled spatially and temporally. However, the investigators noted that the clinical-stage PIT agent cetuximab–IR700 can cause inflammation, swelling, and edema, potentially limiting applications outside oncology.
Activatable PIT Targets T Cells and Tumor Antigens
Kercher and colleagues developed vertamax, a benzoporphyrin-based antibody–photosensitizer conjugate platform engineered to remain quenched until enzymatically activated inside target cells. The investigators evaluated conjugates directed against T-cell antigens CD2 and CD5 and the tumor-associated antigen EGFR.
CD5-directed vertamax-PIT selectively depleted T cells in healthy human skin biopsies. The approach also depleted pathogenic T cells in a biopsy obtained from a single patient with cutaneous T-cell lymphoma. In an in vivo tumor model, EGFR-targeted vertamax-PIT inhibited tumor growth without detectable off-target toxicity, distinguishing its observed effects from IR700-PIT in the experiments.
The authors concluded that vertamax represents a potentially safer alternative PIT platform with possible applications in oncology, autoimmunity, and other diseases in which minimizing inflammation is important.