Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2

Tumor-derived peptides presented by MHC class I molecules are targets for t umor rejection by CD8(+) CTLs. MHC-restricted CD8(+) CTLs are required also for the identification and characterization of tumor antigens that will be useful for immune therapy. For many human solid tumors, however, tumor ant igens remain undefined because of the difficulty of generating MHC-restrict ed, tumor-specific CTLs required for their analysis. CD8(+) CTL responses a re modulated by CD4(+) helper T cells and by antigen-presenting cells. In t his study, highly purified CD8(+) T cells were mixed with tumor cells in pr imary cultures in the absence of any other cells to reduce the complexity o f CTL generation, Tumor cells were transfected with HLA-A1 or HLA-A2 and us ed to stimulate partly matched HLA-A1- or HLA-A2-positive CD8(+) T cells. P artial MHC class I matching of tumor and CD8(+) T cells and omission of oth er cells in primary culture was highly effective in generating MHC class I- restricted CTL to poorly immunogenic small cell lung carcinomas (SCLCs). Cy totoxicity,vas further enhanced by cotransfection of tumor cells with B7.1 (CD80), ICAM-1 (CD54) was not as effective as costimulation, SCLC cells pre sented tumor-specific peptides with HLA-A1 and HLA-A2 and were lysed by A1- or A2-restricted CD8(+) CTLs, A1- and AZ-restricted CD8(+) CTLs detected s hared tumor antigens on unrelated SCLC tumor lines in addition to private a ntigens, The use of direct antigen presentation by MHC class I-transfected tumors to MHC class I-matched CD8(+) T cells is an effective way to generat e MHC class I-restricted CTLs toward poorly immunogenic tumors in vitro, pe rmitting the molecular identification of their tumor antigens.