TCR gene therapy of spontaneous prostate carcinoma requires in vivo T cell activation.
Analogous to the clinical use of recombinant high-affinity Abs, transfer of TCR genes may be used to create a T cell compartment specific for self-Ags to which the endogenous T cell repertoire is immune tolerant. In this study, we show in a spontaneous prostate carcinoma model that the combination of vaccination with adoptive transfer of small numbers of T cells that are genetically modified with a tumor-specific TCR results in a marked suppression of tumor development, even though both treatments are by themselves without effect. These results demonstrate the value of TCR gene transfer to target otherwise nonimmunogenic tumor-associated self-Ags provided that adoptive transfer occurs under conditions that allow in vivo expansion of the TCR-modified T cells.
de Witte
Moniek A
MA
Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
Bendle
Gavin M
GM
van den Boom
Marly D
MD
Coccoris
Miriam
M
Schell
Todd D
TD
Tevethia
Satvir S
SS
van Tinteren
Harm
H
Mesman
Elly M
EM
Song
Ji-Ying
JY
Schumacher
Ton N M
TN
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis / Q000235:genetics; D002999:Clone Cells; D016219:Immunotherapy, Adoptive / Q000379:methods; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage / Q000627:therapeutic use*; D013539:Simian virus 40 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014161:Transduction, Genetic / Q000379:methods; D014615:Vaccinia / Q000276:immunology
D000957:Antigens, Viral, Tumor; D011948:Receptors, Antigen, T-Cell