Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour-associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours.
A long-term-cultured cytotoxic T lymphocyte (CTL) line (E/88) was obtained from splenic lymphocytes of BALB/c (H-2d) mice bearing the weakly immunogenic colonic carcinoma C26. This line was shown to be alpha/beta TCR + V beta 6 + CD3 + CD8 + CD4- and to recognize a common tumour-associated antigen on syngeneic carcinomas and sarcomas in a major-histocompatibility--complex-restricted and T-cell-receptor(TCR)-mediated fashion. The assessment of cytotoxic activity on a panel of 30 normal and neoplastic target cells of differing etiology and histo-type showed that E/88 CTL lysed syngeneic colon carcinomas and some fibrosarcomas but not leukemias, lymphomas or mammary carcinomas. Clones derived from the E/88 line exhibited the same lytic pattern. Moreover, anti-T3, anti-Lyt2.2, anti-alpha/beta TCR and anti-V beta 6 mAbs as well as anti-H-2d antisera abolished cytotoxicity when used in blocking experiments. The therapeutic activity of E/88 CTL upon in vivo transfer was assessed in mice bearing either experimental or spontaneous metastases of C26. In both models therapy with E/88 lymphocytes in combination or not with interleukin-2 was highly effective. Adoptive immunotherapy carried out with two clones obtained from line E/88 showed comparable therapeutic effects. In addition, treatment of syngeneic mice bearing experimental metastases of in vitro E/88-lysable or E/88-resistant tumours, showed that E/88 CTL can eradicate metastases of the former but not of the latter neoplasms. These data indicate that long-term CTL lines recognizing common tumour-associated antigens can be derived from tumour-bearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors.
Rodolfo
M
M
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Bassi
C
C
Salvi
C
C
Parmiani
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell