Cytotoxic T‐Cell Clones Isolated from Ovarian Tumour Infiltrating Lymphocytes Recognize Common Determinants on Non‐Ovarian Tumour Clones

Abstract

CTL-TIL lines have been developed from tumour infiltrating lymphocytes (TIL) from the ascites of patients with ovarian carcinoma, and used to investigate whether common tumour antigens are expressed on allogeneic ovarian tumours epithelial tumour lines derived from colon and pancreatic carcinoma. Three CTL lines expressed preferential cytolytic activity against autologous tumour cells and against certain allogeneic ovarian tumour cells that shared HLA-A2 molecules. Analysis of the target specificity of these CTL lines indicated that they also lysed human colon and pancreatic tumour lines sharing HLA-A2. CTL-TIL clones isolated from these lines were found to lyse HLA-A2+ ovarian, colon and pancreatic tumours, and to recognize clonally distributed common epitopes on pancreas and colon tumour clones. These results indicate that shared tumour antigens can be found among tumours of common epithelial cell origin. These results indicate a novel class of T-cell-definable tumour antigens recognized by tumour-reactive CTL on human tumours and may be significant for understanding of cellular immunity in ovarian cancer, identification of CTL-defined tumour antigens and future adoptive specific immunotherapeutic approaches in ovarian cancer.

Adenoviral delivery of B7–1 (CD80) increases the immunogenicity of human ovarian and cervical carcinoma cells

“…This would need to be studied in an autologous setting through generation of a specific CD4 + and/or CD8 + T cell response. It is already well recorded that a variety of tumour cells express specific antigens including melanoma, [33][34][35] ovary, [20][21][22] breast, 22,36 and cervical carcinoma. 37 It therefore appears possible that B7-1 transfer into tumour cells could be used as a means to generate a cellular vaccine which could then be used to elicit tumour-specific CTL response.…”

“…There are comparatively few reports on immunotherapy applied to ovarian and cervical cancers although it is known that these tumours can serve as targets for T cell responses. [19][20][21][22] …”

Limited heterogeneity in the T-cell receptor V-gene usage in lymphocytes infiltrating human colorectal tumours

“…Several groups have demonstrated autologous tumour-reactive, MHC-restricted tumourinfiltrating T lymphocytes (TILs) derived from malignant melanomas (Herin et al, 1987;Itoh et al, 1988), and similar results have been obtained with TILs from head and neck cancers (Yasumura et al, 1993) and ovarian carcinomas (Ioannides et al, 1993). In vivo, TILs appear to be more effective in adoptive immunotherapy than autologous peripheral blood lymphocytes (PBLs) (Rosenberg et al, 1988), suggestive of a primed population in the tumour area.…”

Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma

“…They did not lyse or respond to allogeneic tumour cells or K562 cells. They were of the CD3^CD8' phenotype in ovarian carcinoma [8,9,[26][27][28] and cither CD3^CD4'^CD8" or CD3'CD4"CD8' phenotype in melanoma [5,7,25]. Blocking experiments using MoAb recognizing the CD3 antigen or the a/^TCR inhibited cytotoxicity at the effector cell level, demonstrating that these cell surface structures were involved in the cytolytic process.…”

“…The intense presence of TIL has been associated in certain tumours with favourable prognosis and increased survival [2][3][4]. TIL from patients with malignant melanoma [5][6][7] or ovarian carcinoma [8,9] can be expanded in culture with recombinant IL-2 (rIL-2) over 1500-fold, and often result in T cell lines exhibiting primarily autologous tumour-specific cytotoxicity [5][6][7][8][9].…”