Abstract:
:To generate non-small cell lung cancer (NSCLC)-reactive lymphocytes, we transfected an HLA-A2-expressing human NSCLC line (1355) with the cDNA encoding the lymphocyte co-stimulatory molecule CD80. Following selection in G418, 1355.7 demonstrated stable cell-surface expression of CD80. Allogeneic mixed lymphocyte tumor cell cultures (MLTCs) were established in 600 IU/ml IL-2 using HLA-A2+ normal donor peripheral blood mononuclear cells (PBMCs) stimulated with 1355-P (parental), 1355.7 or IL-2 alone. In 7 of 9 MLTCs, those stimulated with 1355.7 demonstrated enhanced growth after 30 to 45 days of culture. The predominant lymphocyte to grow in all MLTCs was a CD3+alphabeta+CD4+ T cell. In one case, lymphocytes stimulated with 1355.7 (MLTC 2389.7) exhibited preferential lysis of 1355. MLTC 2389.7 was cloned by limiting dilution, and 2 resultant cloids were shown to be NSCLC-reactive and dependent on both MHC class 1 and CD3 in their recognition of tumor cells. Additionally, allogeneic MLTCs were established using three HLA-A2+ NSCLC patients' PBMC. The predominant lymphocyte to grow in these MLTCs was a CD3+ alphabeta+CD8+ T cell. In cytotoxicity studies, MLTC-UKY25.7 demonstrated preferential lysis of 1355-P, 1355.7 and an HLA-A2+ NSCLC cell line, 1650. Lymphocytes from this MLTC did not lyse K562, Daudi or an HLA-A2- NSCLC cell line, 647. Our data suggest that CD80-expressing NSCLC tumor cells may enhance the generation of specific CTLs in vitro. These CTLs could be important reagents for use in cellular immunotherapy and/or in isolating tumor antigens for potential tumor vaccine development.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Bixby DL,Yannelli JRdoi
10.1002/(sici)1097-0215(19981209)78:6<685::aid-ijcsubject
Has Abstractpub_date
1998-12-09 00:00:00pages
685-94issue
6eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19981209)78:6<685::AID-IJCjournal_volume
78pub_type
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