Adoptive transfer of cytotoxic T-cells for treatment of residual disease after irradiation.
OBJECTIVE
To evaluate whether immunotherapy based on adoptively transferred cytotoxic T-cells (CTL) can improve the antitumour efficacy of irradiation.


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.


CONCLUSIONS
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.
Krause
Mechthild
M
Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany. mechthild.krause@tu-dresden.de
Schmitz
Marc
M
Noessner
Elfriede
E
Skrablin
Petra S A
PS
Wehner
Rebekka
R
Rieber
Ernst-Peter
EP
Baumann
Michael
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000532:radiotherapy* / Q000628:therapy*; D054353:Perforin / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014183:Transplantation, Heterologous
D015789:HLA-A2 Antigen; D054353:Perforin; D007371:Interferon-gamma