PMID- 17852560
OWN - NLM
STAT- MEDLINE
DCOM- 20080307
LR  - 20081121
IS  - 0955-3002 (Print)
IS  - 0955-3002 (Linking)
VI  - 83
IP  - 11-12
DP  - 2007 Nov-Dec
TI  - Adoptive transfer of cytotoxic T-cells for treatment of residual disease after 
      irradiation.
PG  - 827-36
AB  - PURPOSE: To evaluate whether immunotherapy based on adoptively transferred 
      cytotoxic T-cells (CTL) can improve the antitumour efficacy of irradiation. 
      MATERIAL AND METHODS: The experiments were performed using the human squamous 
      cell carcinoma line UT-SCC-15, which expresses human leukocyte antigen (HLA)-A2. 
      The UT-SCC-15 cell-mediated activation of JB4 CTL in terms of interferon 
      (IFN)-gamma secretion and cytotoxic potential was determined by enzyme-linked 
      immunosorbent assay and chromium release assay, the perforin content of JB4 cells 
      by flow cytometry. In vivo, tumours were irradiated with 14 Gy. Subsequently, JB4 
      CTL were injected intra- and peritumourally. Volume doubling times were 
      calculated as a marker of tumour growth delay. RESULTS: UT-SCC-15 tumour cells 
      were well recognized by JB4 CTL in vitro, as indicated by profound IFN-gamma 
      secretion and tumour cell lysis. This response was completely abrogated in the 
      presence of an anti-HLA-A2 antibody. In vivo, adoptive transfer of JB4 CTL after 
      irradiation did not delay tumour growth in comparison to irradiation alone. As a 
      possible underlying mechanism, a loss of perforin content and cytolytic function 
      of the CTL in the absence of interleukin (IL)- 2 or IL-15 was found in vitro. 
      CONCLUSION: HLA-A2-alloreactive JB4 cells efficiently recognize and destroy 
      UT-SCC-15 tumour cells in vitro. However, the intratumoural application of JB4 
      cells after irradiation does not enhance the in vivo effect of radiotherapy 
      alone, which might be caused by the reduced cytotoxic potential of JB4 cells in 
      the absence of IL-2 or IL-15. Thus, co-administration of these cytokines might 
      improve the efficacy of combined irradiation and CTL treatment.
FAU - Krause, Mechthild
AU  - Krause M
AD  - Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav 
      Carus, Technical University of Dresden, Germany. mechthild.krause@tu-dresden.de
FAU - Schmitz, Marc
AU  - Schmitz M
FAU - Noessner, Elfriede
AU  - Noessner E
FAU - Skrablin, Petra S A
AU  - Skrablin PS
FAU - Wehner, Rebekka
AU  - Wehner R
FAU - Rieber, Ernst-Peter
AU  - Rieber EP
FAU - Baumann, Michael
AU  - Baumann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Radiat Biol
JT  - International journal of radiation biology
JID - 8809243
RN  - 0 (HLA-A2 Antigen)
RN  - 126465-35-8 (Perforin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/immunology/radiotherapy/therapy
MH  - Cell Line, Tumor
MH  - Combined Modality Therapy
MH  - Female
MH  - HLA-A2 Antigen/metabolism
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - Interferon-gamma/biosynthesis
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Neoplasms, Experimental/immunology/*radiotherapy/*therapy
MH  - Perforin/metabolism
MH  - T-Lymphocytes, Cytotoxic/*immunology/transplantation
MH  - Transplantation, Heterologous
EDAT- 2007/09/14 09:00
MHDA- 2008/03/08 09:00
CRDT- 2007/09/14 09:00
PHST- 2007/09/14 09:00 [pubmed]
PHST- 2008/03/08 09:00 [medline]
PHST- 2007/09/14 09:00 [entrez]
AID - 781645177 [pii]
AID - 10.1080/09553000701570196 [doi]
PST - ppublish
SO  - Int J Radiat Biol. 2007 Nov-Dec;83(11-12):827-36. doi: 10.1080/09553000701570196.