In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2.
J Clin Oncol
; 12(7): 1475-83, 1994 Jul.
Article
em En
| MEDLINE
| ID: mdl-8021739
ABSTRACT
PURPOSE:
To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. PATIENTS ANDMETHODS:
Forty-one melanoma patients undergoing 43 separate treatment courses with TIL and interleukin-2 (IL-2) from December 1990 through November 1992 were studied prospectively. Multiple patient and treatment characteristics were evaluated for response correlates. In addition, TIL were assayed within 7 days of infusion for characteristics such as doubling time, cell-surface phenotype, autologous tumor lysis in 4-hour chromium-51 release assays, and cytokine secretion following autologous tumor stimulation.RESULTS:
Nine patients experienced complete or partial tumor regressions. Clinical parameters such as age, sex, sites of disease, performance status, and prior therapies were similar in responders and nonresponders. Treatment variables such as the cumulative IL-2 dose and concomitant administration of cyclophosphamide or interferon (IFN)-alpha were not predictive of response, although responders received 33% more TIL. However, statistically significant differences in favor of clinical response were noted for extranodal source of TIL (v lymph node), shorter culture duration (mean, 38 v 47 days), shorter TIL doubling time (2.6 v 3.7 days), greater autologous tumor lysis by TIL (30% v 15%; effector-to-target [ET], 401), and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) by TIL following autologous tumor stimulation (six of nine responders v eight of 32 nonresponders).CONCLUSION:
The associations of TIL lysis of autologous tumor and younger TIL age with clinical response observed in this study are supportive of previous reports, and these findings will be useful in designing future clinical trials. The new observation correlating GM-CSF secretion by TIL with clinical response is interesting and needs further substantiation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos do Interstício Tumoral
/
Interleucina-2
/
Imunoterapia
/
Melanoma
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
1994
Tipo de documento:
Article