Immunotherapy of folate receptor-expressing tumors: Review of recent advances and future prospects

The cell surface receptor for the vitamin folic acid (termed the folate receptor), is often elevated in cancers of the ovary, kidney, lung, mammary gland, brain, endometrium, and myeloid cells of hematopoietic origin. Because the folate receptor (FR) is either absent from normal tissues or localized to the apical surfaces of polarized epithelia, where it is inaccessible to circulating drugs, folate-linked drugs do not normally accumulate in healthy tissues. However, since the same receptor is fully accessible on cancer cells, it has frequently been exploited as a target for receptor-directed cancer therapies, including chemotherapies and immunotherapies. In fact, most strategies for the immunotherapy of cancer have at some time been adapted to treat FR-expressing tumors. In this article, recent progress in the retargeting of the immune system to folate receptor-expressing cancers is summarized and future strategies for redirecting natural killer cells, antibodies and cytotoxic T lymphocytes to this large class of malignancies are proposed.