Adoptive immunotherapy for stage IV renal cell carcinoma

A novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2

John Wang, Alexander Walle, Bruce Gordon, Abraham Novogrodsky, Manikkam Suthanthiran, Albert L. Rubin, Harvey Morrison, Richard T. Silver, Kurt H. Stenzel

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In a pilot study involving 13 patients with advanced stage IV renal cell carcinoma, anti-tumor effects and toxicity of a novel form of adoptive immunotherapy were determined. The protocol utilizes infusions of autologous mononuclear leukocytes treated with the oxidizing mitogen sodium periodate (IO4-) and cultured in medium containing human recombinant interleukin-2 (IL-2), and continuous infusions of low-dose IL-2 (mean ± SD dose = 39.5 ± 8.6 × 103 U/kg/24 hours). Leukocytes (5 to 10 × 109) were removed by leukapheresis three times per week, mononuclear cells were separated, activated with IO4- and cultured in medium containing IL-2 (500 U/ml) for 48 to 72 hours. The cells were re-infused following the next leukapheresis procedure. IL-2 was administered five days per week. Treatment was continued for two three-week cycles. An increase in peripheral blood mononuclear cells bearing the natural killer cell (NK) surface marker, Leu 11, an increase in NK- and antibody-dependent cell-mediated cytotoxicity, and a slight increase in spontaneous cytotoxicity for non-NK targets were noted. Regressions (more than 50 percent decrease in tumor mass) of pulmonary, liver, bone, or soft tissue metastases were induced in six patients. Severe fluid retention did not develop in any patient and no patient required treatment in the intensive care unit. Five of the patients who showed a response have experienced a relapse at 5.2 ± 1.0 (mean ± SD) months. These observations indicate that IO4-/IL-2-activated killer cells plus continuous infusions of low-dose IL-2 can result in regression of metastatic renal cell carcinoma.

Original languageEnglish
Pages (from-to)1016-1023
Number of pages8
JournalThe American Journal of Medicine
Volume83
Issue number6
DOIs
Publication statusPublished - 1 Jan 1987
Externally publishedYes

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Adoptive Immunotherapy
Renal Cell Carcinoma
Interleukin-2
Leukocytes
Leukapheresis
Natural Killer Cells
Antibody-Dependent Cell Cytotoxicity
Mononuclear Leukocytes
Mitogens
Intensive Care Units
metaperiodate
Blood Cells
Neoplasms
Neoplasm Metastasis
Bone and Bones
Recurrence
Lung
Liver
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Adoptive immunotherapy for stage IV renal cell carcinoma : A novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2. / Wang, John; Walle, Alexander; Gordon, Bruce; Novogrodsky, Abraham; Suthanthiran, Manikkam; Rubin, Albert L.; Morrison, Harvey; Silver, Richard T.; Stenzel, Kurt H.

In: The American Journal of Medicine, Vol. 83, No. 6, 01.01.1987, p. 1016-1023.

Research output: Contribution to journalArticle

Wang, John ; Walle, Alexander ; Gordon, Bruce ; Novogrodsky, Abraham ; Suthanthiran, Manikkam ; Rubin, Albert L. ; Morrison, Harvey ; Silver, Richard T. ; Stenzel, Kurt H. / Adoptive immunotherapy for stage IV renal cell carcinoma : A novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2. In: The American Journal of Medicine. 1987 ; Vol. 83, No. 6. pp. 1016-1023.
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