Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele

S Gnjatic, Y Nagata, E Jäger… - Proceedings of the …, 2000 - National Acad Sciences
S Gnjatic, Y Nagata, E Jäger, E Stockert, S Shankara, BL Roberts, GP Mazzara, SY Lee…
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong
CD8+ T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer
patients who can be assessed for immunity to NY-ESO-1, a general method was devised to
detect T cell reactivity independent of prior characterization of epitopes. A recombinant
adenoviral vector encoding the full cDNA sequence of NY-ESO-1 was used to transduce
CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified …
NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong CD8+ T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer patients who can be assessed for immunity to NY-ESO-1, a general method was devised to detect T cell reactivity independent of prior characterization of epitopes. A recombinant adenoviral vector encoding the full cDNA sequence of NY-ESO-1 was used to transduce CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified antigen-presenting cells were then used to restimulate memory effector cells against NY-ESO-1 from the peripheral blood of cancer patients. Specific CD8+ T cells thus sensitized were assayed on autologous B cell targets infected with a recombinant vaccinia virus encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in antibody-positive patients, regardless of their HLA profile. Because the vectors do not cross-react immunologically, only responses to NY-ESO-1 were detected. The approach described here allows monitoring of CD8+ T cell responses to NY-ESO-1 in the context of various HLA alleles and has led to the definition of NY-ESO-1 peptides presented by HLA-Cw3 and HLA-Cw6 molecules.
National Acad Sciences