A study comparing the functional activity of HER2-CAR constructs containing CD28 or 4-1BB intracellular co-stimulatory signal domains found that HER2-CARs with 4-1BB co-stimulatory domains exhibited improved tumor targeting, reduced T cell depletion, and enhanced proliferation ability, making them suitable for treating multifocal brain metastases (27). The gene discussed is ERBB2; the disease is neoplasm.