In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2

Douglas J. Schwartzentruber, Sophia S. Hom, Roya Dadmarz, Donald E. White, John R. Yannelli, Seth M. Steinberg, Steven A. Rosenberg, Suzanne Topalian

Research output: Contribution to journalArticle

Abstract

Purpose: To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. Patients and Methods: 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)-α 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 [E:T], 40:1), 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.

Original languageEnglish (US)
Pages (from-to)1475-1483
Number of pages9
JournalJournal of Clinical Oncology
Volume12
Issue number7
StatePublished - Jul 1994
Externally publishedYes

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Tumor-Infiltrating Lymphocytes
Interleukin-2
Melanoma
Therapeutics
Neoplasms
Granulocyte-Macrophage Colony-Stimulating Factor
In Vitro Techniques
Chromium
Immunotherapy
Cyclophosphamide
Interferons

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schwartzentruber, D. J., Hom, S. S., Dadmarz, R., White, D. E., Yannelli, J. R., Steinberg, S. M., ... Topalian, S. (1994). In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. Journal of Clinical Oncology, 12(7), 1475-1483.

In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. / Schwartzentruber, Douglas J.; Hom, Sophia S.; Dadmarz, Roya; White, Donald E.; Yannelli, John R.; Steinberg, Seth M.; Rosenberg, Steven A.; Topalian, Suzanne.

In: Journal of Clinical Oncology, Vol. 12, No. 7, 07.1994, p. 1475-1483.

Research output: Contribution to journalArticle

Schwartzentruber, DJ, Hom, SS, Dadmarz, R, White, DE, Yannelli, JR, Steinberg, SM, Rosenberg, SA & Topalian, S 1994, 'In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2', Journal of Clinical Oncology, vol. 12, no. 7, pp. 1475-1483.
Schwartzentruber DJ, Hom SS, Dadmarz R, White DE, Yannelli JR, Steinberg SM et al. In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. Journal of Clinical Oncology. 1994 Jul;12(7):1475-1483.
Schwartzentruber, Douglas J. ; Hom, Sophia S. ; Dadmarz, Roya ; White, Donald E. ; Yannelli, John R. ; Steinberg, Seth M. ; Rosenberg, Steven A. ; Topalian, Suzanne. / In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 7. pp. 1475-1483.
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abstract = "Purpose: To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. Patients and Methods: 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)-α 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 [E:T], 40:1), 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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T1 - In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2

AU - Schwartzentruber, Douglas J.

AU - Hom, Sophia S.

AU - Dadmarz, Roya

AU - White, Donald E.

AU - Yannelli, John R.

AU - Steinberg, Seth M.

AU - Rosenberg, Steven A.

AU - Topalian, Suzanne

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N2 - Purpose: To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. Patients and Methods: 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)-α 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 [E:T], 40:1), 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.

AB - Purpose: To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. Patients and Methods: 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)-α 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 [E:T], 40:1), 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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