Adoptive transfer of cytotoxic T-cells for treatment of residual disease after irradiation.

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

Monoclonal antibodies against T-cell antigens studied by immunohistochemistry.

Fifteen monoclonal antibodies against different T-cell antigens were studied by immunohistochemistry in thymus, fetal thymus, fetal liver, palatine tonsils, and a few T-cell lymphomas. OKT 9 was identified as reacting with hemopoietic stem or precursor cells in fetal liver as well as with early B-determined lymphocytes in tonsillar germinal centres. OKT 10 labelled lymphocytes in thymus and surprisingly also the cytoplasm of some tonsillar cells with plasma-cell like appearance. OKT 6 and MAS 036 b reacted only with thymic cells. OKT 4, OKT 5, OKT 8, 8-11, labelled thymic cells- and portions of interfollicular cells in tonsils. OKT 3, NEI 016, NEI 015, and T 28 stained a majority of thymic cells and of tonsillar interfollicular lymphocytes. IFH-M 203, NEI 012 and 4-11 were positive with the majority of T-lymphocytes in tonsils but labelled only a few thymic cells