Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy

Augmentation with cyclophosphamide and correlation with response

Barbara A Pockaj, R. M. Sherry, J. P. Wei, J. R. Yannelli, C. S. Carter, S. F. Leitman, J. A. Carasquillo, S. M. Steinberg, S. A. Rosenberg, J. C. Yang

Research output: Contribution to journalArticle

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Abstract

Background. The adoptive transfer of interleukin-2 [IL-2]-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma. Methods. Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses. Results. Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients whose 111In- labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004% injectate/gram of tissue, respectively; P2 = <0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P = 0.022). Conclusions. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.

Original languageEnglish (US)
Pages (from-to)1731-1737
Number of pages7
JournalCancer
Volume73
Issue number6
StatePublished - 1994
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Adoptive Immunotherapy
Cyclophosphamide
Neoplasms
Radionuclide Imaging
Interleukin-2
Biopsy
Skin
Melanoma
Therapeutics
Adoptive Transfer
Statistical Factor Analysis

Keywords

  • cyclophosphamide
  • immunotherapy
  • melanoma
  • radio imaging
  • tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy : Augmentation with cyclophosphamide and correlation with response. / Pockaj, Barbara A; Sherry, R. M.; Wei, J. P.; Yannelli, J. R.; Carter, C. S.; Leitman, S. F.; Carasquillo, J. A.; Steinberg, S. M.; Rosenberg, S. A.; Yang, J. C.

In: Cancer, Vol. 73, No. 6, 1994, p. 1731-1737.

Research output: Contribution to journalArticle

Pockaj, BA, Sherry, RM, Wei, JP, Yannelli, JR, Carter, CS, Leitman, SF, Carasquillo, JA, Steinberg, SM, Rosenberg, SA & Yang, JC 1994, 'Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy: Augmentation with cyclophosphamide and correlation with response', Cancer, vol. 73, no. 6, pp. 1731-1737.
Pockaj, Barbara A ; Sherry, R. M. ; Wei, J. P. ; Yannelli, J. R. ; Carter, C. S. ; Leitman, S. F. ; Carasquillo, J. A. ; Steinberg, S. M. ; Rosenberg, S. A. ; Yang, J. C. / Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy : Augmentation with cyclophosphamide and correlation with response. In: Cancer. 1994 ; Vol. 73, No. 6. pp. 1731-1737.
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title = "Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy: Augmentation with cyclophosphamide and correlation with response",
abstract = "Background. The adoptive transfer of interleukin-2 [IL-2]-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma. Methods. Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses. Results. Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4{\%}) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8{\%}) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7{\%}) treatment courses without cyclophosphamide. In addition, patients whose 111In- labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004{\%} injectate/gram of tissue, respectively; P2 = <0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5{\%}) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P = 0.022). Conclusions. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.",
keywords = "cyclophosphamide, immunotherapy, melanoma, radio imaging, tumor infiltrating lymphocytes",
author = "Pockaj, {Barbara A} and Sherry, {R. M.} and Wei, {J. P.} and Yannelli, {J. R.} and Carter, {C. S.} and Leitman, {S. F.} and Carasquillo, {J. A.} and Steinberg, {S. M.} and Rosenberg, {S. A.} and Yang, {J. C.}",
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T1 - Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy

T2 - Augmentation with cyclophosphamide and correlation with response

AU - Pockaj, Barbara A

AU - Sherry, R. M.

AU - Wei, J. P.

AU - Yannelli, J. R.

AU - Carter, C. S.

AU - Leitman, S. F.

AU - Carasquillo, J. A.

AU - Steinberg, S. M.

AU - Rosenberg, S. A.

AU - Yang, J. C.

PY - 1994

Y1 - 1994

N2 - Background. The adoptive transfer of interleukin-2 [IL-2]-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma. Methods. Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses. Results. Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients whose 111In- labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004% injectate/gram of tissue, respectively; P2 = <0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P = 0.022). Conclusions. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.

AB - Background. The adoptive transfer of interleukin-2 [IL-2]-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma. Methods. Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses. Results. Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients whose 111In- labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004% injectate/gram of tissue, respectively; P2 = <0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P = 0.022). Conclusions. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.

KW - cyclophosphamide

KW - immunotherapy

KW - melanoma

KW - radio imaging

KW - tumor infiltrating lymphocytes

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