Second-generation (CD28/CD3ζ) and third-generation (CD28/4-1BB/CD3ζ) TEM8-CARs have been engineered to co-target TNBC cells expressing TEM8 as well as tumor-associated vessels, demonstrating the ability to induce TNBC cell regression, as well as to reduce tumor neoangiogenesis in the xenograft mouse model (112, 113). Here, CD28 is linked to neoplasm.