Immunotherapies based on adoptive cell transfer are highly effective in the treatment of metastatic
melanoma, but the use of this approach in other
cancer histologies has been hampered by the identification of appropriate target molecules. Immunologic approaches targeting
tumor vasculature provide a means for the
therapy of multiple solid
tumor types. We developed a method to target
tumor vasculature, using genetically redirected syngeneic or autologous T cells. Mouse and human T cells were engineered to express a
chimeric antigen receptor (CAR) targeted against
VEGFR-2, which is overexpressed in
tumor vasculature and is responsible for
VEGF-mediated
tumor progression and
metastasis. Mouse and human T cells expressing the relevant
VEGFR-2 CARs mediated specific immune responses against
VEGFR-2 protein as well as VEGFR-2-expressing cells in vitro. A single dose of
VEGFR-2 CAR-engineered mouse T cells plus exogenous
IL-2 significantly inhibited the growth of 5 different types of established, vascularized syngeneic
tumors in 2 different strains of mice and prolonged the survival of mice. T cells transduced with
VEGFR-2 CAR showed durable and increased
tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human
cancers.