PMID- 17145892
OWN - NLM
STAT- MEDLINE
DCOM- 20070110
LR  - 20171116
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 23
DP  - 2006 Dec 1
TI  - Superior antitumor in vitro responses of allogeneic matched sibling compared with 
      autologous patient CD8+ T cells.
PG  - 11447-54
AB  - 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.
FAU - Kausche, Sandra
AU  - Kausche S
AD  - Department of Medicine III, Hematology and Oncology, University of Mainz, Mainz, 
      Germany.
FAU - Wehler, Thomas
AU  - Wehler T
FAU - Schnurer, Elke
AU  - Schnurer E
FAU - Lennerz, Volker
AU  - Lennerz V
FAU - Brenner, Walburgis
AU  - Brenner W
FAU - Melchior, Sebastian
AU  - Melchior S
FAU - Grone, Mark
AU  - Grone M
FAU - Nonn, Marion
AU  - Nonn M
FAU - Strand, Susanne
AU  - Strand S
FAU - Meyer, Ralf
AU  - Meyer R
FAU - Ranieri, Elena
AU  - Ranieri E
FAU - Huber, Christoph
AU  - Huber C
FAU - Falk, Christine S
AU  - Falk CS
FAU - Herr, Wolfgang
AU  - Herr W
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD3 Complex)
RN  - 0 (CD8 Antigens)
RN  - 0 (HLA Antigens)
RN  - 126880-86-2 (L-Selectin)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Antibody Specificity/immunology
MH  - CD3 Complex/genetics/immunology
MH  - CD8 Antigens/genetics/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Carcinoma, Renal Cell/genetics/*immunology/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Survival/genetics/immunology
MH  - Cytotoxicity, Immunologic/genetics/immunology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Flow Cytometry
MH  - HLA Antigens/genetics/immunology
MH  - Humans
MH  - Kidney Neoplasms/genetics/*immunology/pathology
MH  - L-Selectin/genetics/immunology
MH  - Lymphocytes, Tumor-Infiltrating/immunology/metabolism
MH  - *Siblings
MH  - T-Lymphocytes, Cytotoxic/immunology/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2006/12/06 09:00
MHDA- 2007/01/11 09:00
CRDT- 2006/12/06 09:00
PHST- 2006/12/06 09:00 [pubmed]
PHST- 2007/01/11 09:00 [medline]
PHST- 2006/12/06 09:00 [entrez]
AID - 66/23/11447 [pii]
AID - 10.1158/0008-5472.CAN-06-0998 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Dec 1;66(23):11447-54. doi: 10.1158/0008-5472.CAN-06-0998.