Int J Cancer. 2006 Jan 31; [Epub ahead of print]
Generation of tumoricidal PAX3 peptide antigen specific cytotoxic T
lymphocytes.
Rodeberg DA, Nuss RA, Elsawa SF, Erskine CL, Celis E.
Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
The transcription factor PAX3 is expressed during early embryogenesis
and in multiple cancer types, including embryonal rhabdomyosarcoma
(ERMS), Ewing sarcoma (ES) and malignant melanoma (MEL), suggesting
that it could function as a general tumor associated antigen. Major
histocompatibility complex (MHC) peptide binding algorithms were used
to predict potential epitopes in PAX3 capable of stimulating in vitro
naive HLA-A0201 restricted cytotoxic T-lymphocytes (CTLs). Two
peptides, PAX3-282 (QLMAFNHLI) and a modified version of this peptide
PAX3-282.9V (QLMAFNHLV), were capable of inducing antigen-specific
CTLs. Of these peptides, PAX3-282.9V was the most efficient inducer of
primary CTL response. These CTLs were able to lyse HLA-A0201 expressing
target cells that were pulsed with peptide, and more importantly, were
effective in killing tumor cells that express PAX3, including ERMS, ES
and MEL cell lines. These findings provide compelling evidence that
peptide PAX3-282 is naturally processed by tumors and is presented in
the context of HLA-A0201 in adequate amounts to allow CTL recognition.
Also, PAX3-282.9V is an effective immunogenic peptide able to induce
CTL recognition of PAX3-containing tumors and may be used as an
antitumor peptide vaccine. (c) 2006 Wiley-Liss, Inc.
PMID: 16450380 [PubMed – as supplied by publisher]