Adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 in patients with metastatic malignant melanoma and renal cell carcinoma: a pilot study
| Autor: | Hong Li, Peter S. Goedegebuure, Timothy J. Eberlein, D. D. Schoof, L. M. Douville, M. Scavone, G. C. Richmond |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Adult
Cytotoxicity Immunologic Male Interleukin 2 Cancer Research Pathology medicine.medical_specialty medicine.medical_treatment Pilot Projects Lymphocyte Activation Immunotherapy Adoptive Gastroenterology Lymphocytes Tumor-Infiltrating Renal cell carcinoma Internal medicine medicine Carcinoma Humans Neoplasm Metastasis Carcinoma Renal Cell Melanoma Aged Epithelioma Tumor-infiltrating lymphocytes business.industry Remission Induction Immunotherapy Middle Aged medicine.disease Kidney Neoplasms Recombinant Proteins Oncology Cytokines Interleukin-2 Female business Progressive disease Muromonab-CD3 medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 13:1939-1949 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.1995.13.8.1939 |
| Popis: | PURPOSE The objective of this study was to determine the tolerance and effect of moderate-dose recombinant human interleukin-2 (rHu IL-2) and tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) refractory to standard therapy. PATIENTS AND METHODS Twenty-six patients (18 MM and eight RCC) were entered onto this pilot study. TIL were isolated from fresh biopsy material and activated with anti-CD3 antibody, OKT3, for 48 hours and expanded in 100 IU/mL r-methionyl Hu IL-2 alanine 125 (r-met Hu IL-2 [ala-125]). At least 10(10) TIL were reinfused intravenously in three divided injections on days 2, 4, and 6 of the protocol. A maximum dose of 30,000 U/kg of IL-2 per injection was administered every 8 hours from day 2 through day 11 for a total of 28 doses. RESULTS Sixteen melanoma patients completed the study. Of these, three (19%) showed a durable complete response (CR), nine (56%) had no response (NR), and four (25%) had progressive disease (PD). One nonresponder demonstrated complete tumor regression within 1 year of treatment. Of four assessable RCC patients, two experienced a minor response (MR) and two showed NR. All TIL cultures showed comparably high cytotoxic activity as determined by antibody-redirected lysis (ARL). More importantly, melanoma TIL from responders possessed significantly higher cytotoxicity against autologous tumor cells than TIL from nonresponders (P < .05). Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-4 was similar for TIL from melanoma responders and nonresponders, or TIL from RCC patients. CONCLUSIONS Immunotherapy with polyclonally activated TIL and moderate-dose IL-2 could be successfully used for the treatment of immunogenic tumors with less toxicity and lower costs as compared with high-dose IL-2 protocols. |
| Databáze: | OpenAIRE |
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