TY - JOUR
T1 - Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour-associated antigen
T2 - The pattern of in vitro reactivity predicts the in vivo effect on different tumours
AU - Rodolfo, Monica
AU - Bassi, Cinzia
AU - Salvi, Carolina
AU - Parmiani, Giorgio
PY - 1991/1
Y1 - 1991/1
N2 - 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 α/βTCR+Vβ6+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 histotype 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-α/βTCR and anti-Vβ6 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 tumourbearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors.
AB - 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 α/βTCR+Vβ6+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 histotype 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-α/βTCR and anti-Vβ6 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 tumourbearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors.
KW - Adoptive immunotherapy
KW - Common tumour-associated antigens
KW - Cytotoxic T cell line
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U2 - 10.1007/BF01741325
DO - 10.1007/BF01741325
M3 - Article
C2 - 1760812
AN - SCOPUS:0026062931
VL - 34
SP - 53
EP - 62
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 1
ER -