Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: A pilot study

Suzanne Topalian, D. Solomon, F. P. Avis, A. E. Chang, D. L. Freerksen, W. M. Linehan, M. T. Lotze, C. N. Robertson, C. A. Seipp, P. Simon, C. G. Simpson, S. A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 x 109 to 2.3 x 1011 cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

Original languageEnglish (US)
Pages (from-to)839-853
Number of pages15
JournalJournal of Clinical Oncology
Volume6
Issue number5
StatePublished - 1988
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Immunotherapy
Interleukin-2
Lymphokine-Activated Killer Cells
Neoplasms
Adoptive Immunotherapy
Melanoma
Poisons
Renal Cell Carcinoma
Breast Neoplasms
Adoptive Transfer
Lymphocyte Subsets
Lymph
Chromium
Pleural Effusion
Skin Diseases
Interleukin-10
Cyclophosphamide
Colon
Lymph Nodes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Topalian, S., Solomon, D., Avis, F. P., Chang, A. E., Freerksen, D. L., Linehan, W. M., ... Rosenberg, S. A. (1988). Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: A pilot study. Journal of Clinical Oncology, 6(5), 839-853.

Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2 : A pilot study. / Topalian, Suzanne; Solomon, D.; Avis, F. P.; Chang, A. E.; Freerksen, D. L.; Linehan, W. M.; Lotze, M. T.; Robertson, C. N.; Seipp, C. A.; Simon, P.; Simpson, C. G.; Rosenberg, S. A.

In: Journal of Clinical Oncology, Vol. 6, No. 5, 1988, p. 839-853.

Research output: Contribution to journalArticle

Topalian, S, Solomon, D, Avis, FP, Chang, AE, Freerksen, DL, Linehan, WM, Lotze, MT, Robertson, CN, Seipp, CA, Simon, P, Simpson, CG & Rosenberg, SA 1988, 'Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: A pilot study', Journal of Clinical Oncology, vol. 6, no. 5, pp. 839-853.
Topalian, Suzanne ; Solomon, D. ; Avis, F. P. ; Chang, A. E. ; Freerksen, D. L. ; Linehan, W. M. ; Lotze, M. T. ; Robertson, C. N. ; Seipp, C. A. ; Simon, P. ; Simpson, C. G. ; Rosenberg, S. A. / Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2 : A pilot study. In: Journal of Clinical Oncology. 1988 ; Vol. 6, No. 5. pp. 839-853.
@article{4890787d31f74f22953c565eff3bbd84,
title = "Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: A pilot study",
abstract = "Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 x 109 to 2.3 x 1011 cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.",
author = "Suzanne Topalian and D. Solomon and Avis, {F. P.} and Chang, {A. E.} and Freerksen, {D. L.} and Linehan, {W. M.} and Lotze, {M. T.} and Robertson, {C. N.} and Seipp, {C. A.} and P. Simon and Simpson, {C. G.} and Rosenberg, {S. A.}",
year = "1988",
language = "English (US)",
volume = "6",
pages = "839--853",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "5",

}

TY - JOUR

T1 - Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2

T2 - A pilot study

AU - Topalian, Suzanne

AU - Solomon, D.

AU - Avis, F. P.

AU - Chang, A. E.

AU - Freerksen, D. L.

AU - Linehan, W. M.

AU - Lotze, M. T.

AU - Robertson, C. N.

AU - Seipp, C. A.

AU - Simon, P.

AU - Simpson, C. G.

AU - Rosenberg, S. A.

PY - 1988

Y1 - 1988

N2 - Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 x 109 to 2.3 x 1011 cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

AB - Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 x 109 to 2.3 x 1011 cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.

UR - http://www.scopus.com/inward/record.url?scp=0023934650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023934650&partnerID=8YFLogxK

M3 - Article

C2 - 3259261

AN - SCOPUS:0023934650

VL - 6

SP - 839

EP - 853

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 5

ER -