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Kausche, S.* ; Wehler, T.* ; Schnürer, E.* ; Lennerz, V.* ; Brenner, W.* ; Melchior, S.* ; Gröne, M.* ; Nonn, M.* ; Strand, S.* ; Meyer, R.* ; Ranieri, E.* ; Huber, C.* ; Falk, C.S. ; Herr, W.*

Superior antitumor in vitro responses of allogeneic matched sibling compared with autologous patient CD8plus T cells.

Cancer Res. 66, 11447-11454 (2006)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Allogeneic cell therapy as a means to break immunotolerance to solid tumors is increasingly used for cancer treatment. To investigate cellular alloimmune responses in a human tumor model, primary cultures were established from renal cell carcinoma (RCC) tissues of 56 patients. In three patients with stable RCC line and human leukocyte antigen (HLA)-identical sibling donor available, allogeneic and autologous RCC reactivities were compared using mixed lymphocyte/tumor cell cultures (MLTC). Responding lymphocytes were exclusively CD8(+) T cells, whereas CD4(+) T cells or natural killer cells were never observed. Sibling MLTC populations showed higher proliferative and cytolytic antitumor responses compared with their autologous counterparts. The allo-MLTC responders originated from the CD8(+) CD62L(high)(+) peripheral blood subpopulation containing naive precursor and central memory T cells. Limiting dilution cloning failed to establish CTL clones from autologous MLTCs or tumor-infiltrating lymphocytes. In contrast, a broad panel of RCC-reactive CTL clones was expanded from each allogeneic MLTC. These sibling CTL clones either recognized exclusively the original RCC tumor line or cross-reacted with nonmalignant kidney cells of patient origin. A minority of CTL clones also recognized patient-derived hematopoietic cells or other allogeneic tumor targets. The MHC-restricting alleles for RCC-reactive sibling CTL clones included HLA-A2, HLA-A3, HLA-A11, HLA-A24, and HLA-B7. In one sibling donor-RCC pair, strongly proliferative CD3(+)CD16(+)CD57(+) CTL clones with non-HLA-restricted antitumor reactivity were established. Our results show superior tumor-reactive CD8 responses of matched allogeneic compared with autologous T cells. These data encourage the generation of antitumor T-cell products from HLA-identical siblings and their potential use in adoptive immunotherapy of metastatic RCC patients.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2006
HGF-Berichtsjahr 0
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Zeitschrift Cancer Research
Quellenangaben Band: 66, Heft: 23, Seiten: 11447-11454 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia, Pa.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501700-006
Erfassungsdatum 2007-11-27
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