TY - JOUR
T1 - Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2
AU - Arienti, Flavio
AU - Belli, Filiberto
AU - Rivoltini, Licia
AU - Gambacorti-Passerini, Carlo
AU - Furlan, Luigi
AU - Mascheroni, Luigi
AU - Prada, Augusto
AU - Rizzi, Maurilia
AU - Marchesi, Edoardo
AU - Vaglini, Maurizio
AU - Parmiani, Giorgio
AU - Cascinelli, Natale
PY - 1993/9
Y1 - 1993/9
N2 - Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogeneic tumor cells. A preferential lysis of autologous melanoma cells was obtained in long-term cultures of 7/13 cases (54%), while the remaining ones showed a major-histocompatibility-complex-unrestricted, lymphokine-activated-killer(LAK)-like activity at the time of in vivo injection. Sixteen patients with metastatic melanoma were infused with TIL (mean number: 6.8×109, range: 0.35 × 109-20 × 109) and IL-2 (mean dose: 130 × 106 IU, range: 28.8 × 106-231 × 106 IU); 1 complete and 3 partial responses were observed in 12 evaluable patients (response rate 33%). In all responding patients, injected TIL showed an in vitro preferential lysis of autologous tumor cells, while in no cases were TIL with LAK-like activity associated with a clinical response. The mean autologous tumor cytotoxic activity of TIL at the time of in vivo injection was significantly higher in responding patients in comparison to nonresponding ones, suggesting that a marked and preferential cytolysis of autologous tumor cells is associated with the therapeutic efficacy of TIL.
AB - Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogeneic tumor cells. A preferential lysis of autologous melanoma cells was obtained in long-term cultures of 7/13 cases (54%), while the remaining ones showed a major-histocompatibility-complex-unrestricted, lymphokine-activated-killer(LAK)-like activity at the time of in vivo injection. Sixteen patients with metastatic melanoma were infused with TIL (mean number: 6.8×109, range: 0.35 × 109-20 × 109) and IL-2 (mean dose: 130 × 106 IU, range: 28.8 × 106-231 × 106 IU); 1 complete and 3 partial responses were observed in 12 evaluable patients (response rate 33%). In all responding patients, injected TIL showed an in vitro preferential lysis of autologous tumor cells, while in no cases were TIL with LAK-like activity associated with a clinical response. The mean autologous tumor cytotoxic activity of TIL at the time of in vivo injection was significantly higher in responding patients in comparison to nonresponding ones, suggesting that a marked and preferential cytolysis of autologous tumor cells is associated with the therapeutic efficacy of TIL.
KW - Immunotherapy
KW - Interleukin-2
KW - Melanoma
KW - Tumor-infiltrating lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=0027408443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027408443&partnerID=8YFLogxK
U2 - 10.1007/BF01741170
DO - 10.1007/BF01741170
M3 - Article
C2 - 8477417
AN - SCOPUS:0027408443
VL - 36
SP - 315
EP - 322
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 5
ER -