Targeting self-antigens through allogeneic TCR gene transfer.
Adoptive transfer of T-cell receptor (TCR) genes has been proposed as an attractive approach for immunotherapy in cases where the endogenous T-cell repertoire is insufficient. While there are promising data demonstrating the capacity of TCR-modified T cells to react to foreign antigen encounter, the feasibility of targeting tumor-associated self-antigens has not been addressed. Here we demonstrate that T-cell receptor gene transfer allows the induction of defined self-antigen-specific T-cell responses, even when the endogenous T-cell repertoire is nonreactive. Furthermore, we show that adoptive transfer of T-cell receptor genes can be used to induce strong antigen-specific T-cell responsiveness in partially MHC-mismatched hosts without detectable graft versus host disease. These results demonstrate the feasibility of using a collection of "off the shelf" T-cell receptor genes to target defined tumor-associated self-antigens and thereby form a clear incentive to test this immunotherapeutic approach in a clinical setting.
de Witte
Moniek A
MA
Department of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
Coccoris
Miriam
M
Wolkers
Monika C
MC
van den Boom
Marly D
MD
Mesman
Elly M
EM
Song
Ji-Ying
JY
van der Valk
Martin
M
Haanen
John B A G
JB
Schumacher
Ton N M
TN
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D006086:Graft vs Host Disease; D007167:Immunotherapy / Q000379:methods*; D008285:Major Histocompatibility Complex; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage* / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell