IL-21 promotes the expansion of CD27+CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells

Autor: Daniel J. Powell, Erik Hooijberg, Annelies W. Turksma, Tanja D. de Gruijl, S. Albelda, Megan M. Suhoski, Alfons J.M. van den Eertwegh, Anita G.M. Stam, Carl H. June, Winald R. Gerritsen, Rik J. Scheper, Saskia J. A. M. Santegoets
Přispěvatelé: Medical oncology laboratory, Pathology, Medical oncology, CCA - Immuno-pathogenesis
Rok vydání: 2013
Předmět:
Adoptive cell transfer
Biopsy
medicine.medical_treatment
T cell
Enzyme-Linked Immunosorbent Assay
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Biology
T-Lymphocytes
Regulatory
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
0302 clinical medicine
CD28 Antigens
Immune Regulation [NCMLS 2]
Neoplasms
medicine
Humans
Cytotoxic T cell
Cell Proliferation
030304 developmental biology
Medicine(all)
0303 health sciences
Biochemistry
Genetics and Molecular Biology(all)
Tumor-infiltrating lymphocytes
Research
Interleukins
Receptors
IgG
CD28
General Medicine
Flow Cytometry
Autologous tumor cell
Tumor Necrosis Factor Receptor Superfamily
Member 7
Phenotype
Cytokine
medicine.anatomical_structure
030220 oncology & carcinogenesis
Immunology
Cytokines
K562 Cells
CD8
Zdroj: Journal of Translational Medicine, 11, pp. 37
Journal of Translational Medicine, 11, 37-37. BioMed Central
Journal of Translational Medicine
Santegoets, S J A M, Turksma, A W, Suhoski, M M, Stam, A G M, Albelda, S M, Hooijberg, E, Scheper, R J, van den Eertwegh, A J M, Gerritsen, W R, Powell, D J J, June, C H & de Gruijl, T D 2013, ' IL-21 promotes the expansion of CD27+CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells ', Journal of Translational Medicine, vol. 11, pp. 37-37 . https://doi.org/10.1186/1479-5876-11-37
Journal of Translational Medicine, 11, 37
ISSN: 1479-5876
Popis: Contains fulltext : 118572.pdf (Publisher’s version ) (Open Access) BACKGROUND: Adoptive cell transfer of tumor infiltrating lymphocytes has shown clinical efficacy in the treatment of melanoma and is now also being explored in other tumor types. Generation of sufficient numbers of effector T cells requires extensive ex vivo expansion, often at the cost of T cell differentiation and potency. For the past 20 years, IL-2 has been the key cytokine applied in the expansion of TIL for ACT. However, the use of IL-2 has also led to collateral expansion of regulatory T cells (Tregs) and progressive T cell differentiation, factors known to limit in vivo persistence and activity of transferred TIL. The use of alternative T cell growth factors is therefore warranted. Here, we have compared the effects of IL-2, -15 and -21 cytokines on the expansion and activation of TIL from single-cell suspensions of non-small cell lung cancer, ovarian cancer and melanoma. METHODS: We applied the K562-based artificial APC (aAPC) platform for the direct and rapid expansion of tumor infiltrating lymphocytes isolated from primary cancer specimens. These aAPC were engineered to express the Fc-gamma receptor CD32 (for anti-CD3 antibody binding), the co-stimulatory molecule 4-1BBL, and to secrete either IL-2, IL-15 or IL-21 cytokine. RESULTS: Although IL-2 aAPC induced the greatest overall TIL expansion, IL-21 aAPC induced superior expansion of CD8+ T cells with a CD27+CD28+ "young" phenotype and superior functional cytotoxic effector characteristics, without collateral expansion of Tregs. CONCLUSION: Our data rationalize the clinical application of IL-21-secreting aAPC as a standardized cell-based platform in the expansion of "young" effector TIL for ACT.
Databáze: OpenAIRE
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