Folate-mediated targeting of T cells to tumors.
Recently various strategies have been developed to exploit in a clinical setting the well established finding that T cells can specifically recognize and destroy tumor cells. Several independent approaches to the targeting of T cells against cancer have been explored, including the use of bispecific antibodies (anti-T cell/anti-tumor cell) to redirect T cells, vaccines to induce tumor-reactive T cells, and adoptive transfer of ex vivo activated, tumor-reactive T cells. In this review, we focus on studies in which high-affinity folate receptors (FRs) on tumor cells have served as targets for redirecting or enhancing the effectiveness of activated T cells. Bispecific antibody conjugates of folate and antibodies to the T cell receptor (TCR) complex can generate tumor-reactive T cell responses. The development of folate/antibody conjugates specific for the T cell co-stimulatory molecule CD28 could yield activated T cells that recognize endogenous peptide-major histocompatibility complex (MHC) antigens on tumor cells. Finally, we discuss a less investigated area in which high-affinity FRs on macrophages, or other antigen presenting cells (APCs), may provide opportunities in the design of tumor-antigen-specific vaccines.
Roy
Edward J
EJ
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Gawlick
Ute
U
Orr
Brent A
BA
Kranz
David M
DM
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid