B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models

Area of Science:

• Oncology
• Radiochemistry
• Immunotherapy

Background:

• B7-H4 is an immune checkpoint protein overexpressed in many solid tumors.
• Its limited expression in normal tissues makes it an ideal target for cancer therapy and imaging.

Purpose of the Study:

• To develop and evaluate a B7-H4-targeted radiotheranostic antibody for PET imaging and radionuclide therapy.
• To assess the efficacy and safety of this targeted approach in preclinical models.

Main Methods:

• Development of a B7-H4 antibody conjugated with Zirconium-89 ([89Zr]) for PET imaging.
• Conjugation of the antibody with Lutetium-177 ([177Lu]) or Actinium-225 ([225Ac]) for beta or alpha particle therapy.
• Evaluation of imaging capabilities and therapeutic efficacy in B7-H4 expressing xenografts.

Main Results:

• [89Zr]-immunoPET provided quantitative, whole-body visualization of B7-H4 expression, differentiating tumor burdens.
• Therapy with [177Lu]- or [225Ac]-conjugated antibody showed significant, antigen-dependent tumor regression, including complete and durable responses.
• Therapeutic constructs were well-tolerated, with only transient myelosuppression and no significant organ toxicity.

Conclusions:

• B7-H4 is a promising target for integrated imaging and radionuclide therapy.
• The developed B7-H4-directed radiotheranostic antibody offers a potential new strategy for cancer treatment.