uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Treatment of malignant melanoma patients with expanded tumor-infiltrating T cells and low dose IL-2
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]


Purpose: The prognosis for patients with metastasized malignant melanoma is very poor, and an effective therapy is warranted. Previous studies of adoptive T cell transfer have been encouraging, but have sometimes exhibited severe side effects. We sought to refine earlier applied protocols by using low-dose instead of high-dose IL-2 as a supporting cytokine.  

Experimental design: We evaluated the adoptive transfer of autologous T cells in combination with low-dose s.c. IL-2 in 28 melanoma patients with advanced disease. The patients had progressed on standard treatments. They were pretreated with high-dose chemotherapy for obtaining lymphodepletion to augment the anti-tumor function of the transferred T cells.

Results: The objective response rate was18 %. One patient obtained a long-lasting complete remission and four patients a partial response. Tumor regression was demonstrated in six further patients (21 %) without reaching the RECIST criteria for a partial response.

Conclusions: This is the first study in cancer patients with autologous T cell transfer combined with low-dose s.c. IL-2. The results are promising but modifications of the protocol are needed to increase the response rate. 

National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-139190OAI: oai:DiVA.org:uu-139190DiVA: diva2:380694
Available from: 2010-12-22 Created: 2010-12-22 Last updated: 2011-03-11
In thesis
1. Adoptive T Cell Therapy for Treatment of Metastatic Melanoma
Open this publication in new window or tab >>Adoptive T Cell Therapy for Treatment of Metastatic Melanoma
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malignant melanoma is a common type of solid tumor that causes high cancer-related mortality in young adults of Northern Europe. The incidence of melanoma increases rapidly which renders us a special responsibility to investigate this disease in depth. One recent promising approach to treat malignant melanoma is adoptive cell therapy with tumor-directed autologous T cells. This thesis aims to improve this therapy in four different studies. We first sought to establish a protocol for the assessment of melanoma-specific T-cell cultures in order to screen for optimal specificity and reactivity in a robust, reliable and simple manner. The conclusion was that reactive cells could be found in a majority of patients and could be screened for specificity by stimulation with melanoma cell lines.

In the next study, 28 melanoma patients with advanced disease were treated with autologous tumor-infiltrating T cells. Objective responses (18%) including one sustained complete response were observed. This is the first study in cancer patients with autologous T cell transfer combined with low-dose s.c. IL-2 as supportive cytokine.

In the following two studies we wanted to improve management and culture conditions of the T cells. When investigating methods for improved handling and preservation of large numbers of T cells, we observed that freeze-thawing of T cells could impair the metabolic activity of the T cells. Another conclusion was that rapid expansion of T cells could lead to loss of antigenic specificity and apoptosis. These adverse effects could be prevented with short time recovery. In order to improve expansion methods, mass expansion of T cells in an automated bioreactor was evaluated. We concluded that the bioreactor is suitable for this task and allows for higher cell densities and absolute cell numbers compared to traditional culturing conditions without influencing cell phenotype or reactivity. Taken together, my current studies present guiding principles and encouragement for the further development of immunotherapies for treatment of patients with malignant melanoma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 52 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 637
Malignant melanoma, Adoptive cell therapy
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-143698 (URN)978-91-554-7991-6 (ISBN)
Public defence
2011-03-08, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjöldsväg 20, Uppsala, 09:00 (English)
Available from: 2011-02-14 Created: 2011-01-24 Last updated: 2011-03-11Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Sadeghi, Arian
By organisation
Clinical Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 201 hits
ReferencesLink to record
Permanent link

Direct link