Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy

Richard W. Joseph, Vijay R. Peddareddigari, Ping Liu, Priscilla W. Miller, Willem W. Overwijk, Nebiyou B. Bekele, Merrick I. Ross, Jeffrey E. Lee, Jeffrey E. Gershenwald, Anthony Lucci, Victor G. Prieto, John D. McMannis, Nicholas Papadopoulos, Kevin Kim, Jade Homsi, Agop Bedikian, Wen Jen Hwu, Patrick Hwu, Laszlo G. Radvanyi

Research output: Contribution to journalArticle

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Abstract

Purpose: Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors. Experimental Design: We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment). Results: Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; P = 0.01) and female patients (71% vs. 57% for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% vs. 71%, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (P < 0.0001). Conclusion: Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT.

Original languageEnglish (US)
Pages (from-to)4882-4891
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2011

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Tumor-Infiltrating Lymphocytes
Cell- and Tissue-Based Therapy
Melanoma
Neoplasm Metastasis
T-Lymphocytes
Neoplasms
Lymphocyte Count
Research Design
Therapeutics
Clinical Trials
Lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy. / Joseph, Richard W.; Peddareddigari, Vijay R.; Liu, Ping; Miller, Priscilla W.; Overwijk, Willem W.; Bekele, Nebiyou B.; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Prieto, Victor G.; McMannis, John D.; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen Jen; Hwu, Patrick; Radvanyi, Laszlo G.

In: Clinical Cancer Research, Vol. 17, No. 14, 15.07.2011, p. 4882-4891.

Research output: Contribution to journalArticle

Joseph, RW, Peddareddigari, VR, Liu, P, Miller, PW, Overwijk, WW, Bekele, NB, Ross, MI, Lee, JE, Gershenwald, JE, Lucci, A, Prieto, VG, McMannis, JD, Papadopoulos, N, Kim, K, Homsi, J, Bedikian, A, Hwu, WJ, Hwu, P & Radvanyi, LG 2011, 'Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy', Clinical Cancer Research, vol. 17, no. 14, pp. 4882-4891. https://doi.org/10.1158/1078-0432.CCR-10-2769
Joseph, Richard W. ; Peddareddigari, Vijay R. ; Liu, Ping ; Miller, Priscilla W. ; Overwijk, Willem W. ; Bekele, Nebiyou B. ; Ross, Merrick I. ; Lee, Jeffrey E. ; Gershenwald, Jeffrey E. ; Lucci, Anthony ; Prieto, Victor G. ; McMannis, John D. ; Papadopoulos, Nicholas ; Kim, Kevin ; Homsi, Jade ; Bedikian, Agop ; Hwu, Wen Jen ; Hwu, Patrick ; Radvanyi, Laszlo G. / Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 14. pp. 4882-4891.
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title = "Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy",
abstract = "Purpose: Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50{\%} in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors. Experimental Design: We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment). Results: Overall, initial TIL outgrowth was successful in 62{\%} of patients, with patients ≤30 years of age (94{\%}; P = 0.01) and female patients (71{\%} vs. 57{\%} for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47{\%} vs. 71{\%}, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16{\%} (P < 0.0001). Conclusion: Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT.",
author = "Joseph, {Richard W.} and Peddareddigari, {Vijay R.} and Ping Liu and Miller, {Priscilla W.} and Overwijk, {Willem W.} and Bekele, {Nebiyou B.} and Ross, {Merrick I.} and Lee, {Jeffrey E.} and Gershenwald, {Jeffrey E.} and Anthony Lucci and Prieto, {Victor G.} and McMannis, {John D.} and Nicholas Papadopoulos and Kevin Kim and Jade Homsi and Agop Bedikian and Hwu, {Wen Jen} and Patrick Hwu and Radvanyi, {Laszlo G.}",
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T1 - Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy

AU - Joseph, Richard W.

AU - Peddareddigari, Vijay R.

AU - Liu, Ping

AU - Miller, Priscilla W.

AU - Overwijk, Willem W.

AU - Bekele, Nebiyou B.

AU - Ross, Merrick I.

AU - Lee, Jeffrey E.

AU - Gershenwald, Jeffrey E.

AU - Lucci, Anthony

AU - Prieto, Victor G.

AU - McMannis, John D.

AU - Papadopoulos, Nicholas

AU - Kim, Kevin

AU - Homsi, Jade

AU - Bedikian, Agop

AU - Hwu, Wen Jen

AU - Hwu, Patrick

AU - Radvanyi, Laszlo G.

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Purpose: Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors. Experimental Design: We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment). Results: Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; P = 0.01) and female patients (71% vs. 57% for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% vs. 71%, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (P < 0.0001). Conclusion: Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT.

AB - Purpose: Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors. Experimental Design: We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment). Results: Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; P = 0.01) and female patients (71% vs. 57% for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% vs. 71%, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (P < 0.0001). Conclusion: Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT.

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