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Titolo:
ADJUVANT ADAPTIVE IMMUNOTHERAPY WITH TUMOR-INFILTRATING LYMPHOCYTES AND MODULATED DOSES OF INTERLEUKIN-2 IN 22 PATIENTS WITH MELANOMA, COLORECTAL AND RENAL-CANCER, AFTER RADICAL METASTASECTOMY, AND IN 12 ADVANCED PATIENTS
Autore:
RIDOLFI R; FLAMINI E; RICCOBON A; DEPAOLA F; MALTONI R; GARDINI A; RIDOLFI L; MEDRI L; POLETTI G; AMADORI D;
Indirizzi:
MORGAGNI PIERANTONI HOSP,DEPT MED ONCOL,VIALE FORLANINI I-47100 FORLIITALY IST ONCOL ROMAGNOLO FORLI ITALY MORGAGNI PIERANTONI HOSP,DEPT PATHOL FORLI ITALY MORGAGNI PIERANTONI HOSP,DEPT LAB MED FORLI ITALY
Titolo Testata:
Cancer immunology and immunotherapy
fascicolo: 4, volume: 46, anno: 1998,
pagine: 185 - 193
SICI:
0340-7004(1998)46:4<185:AAIWTL>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEIVING ADOPTIVE IMMUNOTHERAPY; EPITHELIAL OVARIAN-CANCER; CELL LUNG-CARCINOMA; METASTATIC MELANOMA; RECOMBINANT INTERLEUKIN-2; RANDOMIZED TRIAL; NK CELLS; T-CELLS; INFUSION; THERAPY;
Keywords:
ADOPTIVE IMMUNOTHERAPY; INTERLEUKIN-2; TUMOR-INFILTRATING LYMPHOCYTES; ZETA CHAIN-P56(LCK);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
R. Ridolfi et al., "ADJUVANT ADAPTIVE IMMUNOTHERAPY WITH TUMOR-INFILTRATING LYMPHOCYTES AND MODULATED DOSES OF INTERLEUKIN-2 IN 22 PATIENTS WITH MELANOMA, COLORECTAL AND RENAL-CANCER, AFTER RADICAL METASTASECTOMY, AND IN 12 ADVANCED PATIENTS", Cancer immunology and immunotherapy, 46(4), 1998, pp. 185-193

Abstract

Adoptive tumour infiltrating lymphocytes (TIL) in combination with a modulated dosage of interleukin-2 (IL-2) can be used with acceptable toxicity in the treatment of immunogenic tumours. Following an experience of reinfusion in advanced melanoma, colorectal and renal cancer patients, treatment was given to disease-free patients after metastasectomy. The high risk of relapse and favour able ratio between reinfused TTL and possible microscopic residual disease determined this choice ofadjuvant treatment. A group of 12 patients with advanced disease (7 melanoma, 4 colorectal carcinoma, 1 kidney carcinoma) were treated withTIL (median 5.8x10(10) cells) and IL-2 (West's schedule) modulated towards a lower dosage (from 12 to 6 MIU/day) in order to maintain an acceptable level of toxicity. As treatment was well tolerated, it was offered to another 22 patients in an adjuvant setting after metastasectomy (11 melanoma, 10 colorectal carcinoma, 1 renal cancer), the median dose of TIL reinfused being 4.95 x 10(10) cells. No objective responsewas observed in advanced patients: all patients progressed after a median of 1.5 months (0-8 months) and median survival was 8 months (3-22 months). Thirteen patients from the second group are still disease-free after a median of 23+ months (9+-47+ months). The remaining 9 patients relapsed after a median of 5 months (3-18 months). Toxicity was moderate as clinical and hepatic/renal function parameters were used toassess the need for dose reductions. Consequently, there was great diversity in IL-2 dosages administered. In particular, there seemed to be a difference in IL-2 doses administered between disease-free cases and those who progressed (17.5 MIU/day versus 7 MIL/day in melanoma patients; 11.2 MIU/day versus 7.1 MIU/day in colorectal cancer patients). By contrast, no differences were observed between number of TIL reinfused and clinical response. Phenotypical characteristics of reinfused TIL were similar to those reported in the literature: 97% were CD3 and92% were CD8. Aspecific cytolytic activity was evaluated on 12 cases whereas, in 2 melanoma cases, autologous tumour tissue was available for the specific cytotoxicity test. Perforin levels in TIL measured at the end of culture were generally high or very high. Cytokine levels were measured on the supernatant at the end of culture, with an estremevariability in results. Finally, zeta chain and p56(lck) were histologically assessed on the resected tissue from which TIL were cultivated. There were virtually none of the former and a complete absence of the latter, which concurs with data reported in the literature. The sameimmunocytochemical analysis was carried out on TIL at the end of culture. This time an almost complete restoration of both functions was seen, especially in melanoma patients, who are still free from disease. The study is on-going and it has been decided to focus on disease-freepatients after metastasectomy in order to increase the number and possibility of clinical and histological correlations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 03:17:34