The scientific basis for the immunotherapy of human malignant mesothelioma

Robinson, B. W. S., Manning, L. S., Bowman, R. V., Christmas, T. I., Musk, A. W., Davis, M. R., Bielefeldt-Ohmann, H., Upham, J. and Garlepp, M. J. (1993). The scientific basis for the immunotherapy of human malignant mesothelioma. In: Proceedings of the International Conference on Mesothelial Cell and Mesothelioma: Past, Present and Future. International Conference on Mesothelial Cell and Mesothelioma: Past, Present and Future, Paris, France, (195-198). 20 September - 2 October 1991.

Author Robinson, B. W. S.
Manning, L. S.
Bowman, R. V.
Christmas, T. I.
Musk, A. W.
Davis, M. R.
Bielefeldt-Ohmann, H.
Upham, J.
Garlepp, M. J.
Title of paper The scientific basis for the immunotherapy of human malignant mesothelioma
Conference name International Conference on Mesothelial Cell and Mesothelioma: Past, Present and Future
Conference location Paris, France
Conference dates 20 September - 2 October 1991
Proceedings title Proceedings of the International Conference on Mesothelial Cell and Mesothelioma: Past, Present and Future   Check publisher's open access policy
Journal name European Respiratory Review   Check publisher's open access policy
Place of Publication European Respiratory Society
Publisher Lausanne, Switzerland
Publication Year 1993
Sub-type Fully published paper
Open Access Status Not Open Access
ISSN 0905-9180
1600-0617
Volume 3
Issue 11
Start page 195
End page 198
Total pages 3
Language eng
Abstract/Summary The development of immunotherapeutic protocols for the treatment of malignant mesothelioma, a tumour that is resistant to conventional forms of therapy, requires the development of a sound scientific understanding of the relationship between malignant mesothelioma cells and the immune system. Initially we developed a panel of five human mesothelioma cell lines which have been fully characterized, for in vitro and heterotransplant studies. Using these cell lines we have demonstrated that mesothelioma cells are resistant to natural killer (NK) lysis but susceptible to lymphokine-activated killer (LAK) lysis. In addition, we have demonstrated in vitro sensitivity to a number of cytokines, including tumour necrosis factor and the interferons. All human mesothelioma cell lines express immune recognition molecules of the human leucocyte antigen (HLA) class I family and in some cell lines class II molecules can be induced. We then developed an animal model to further evaluate these processes in vivo. Following intraperitoneal asbestos injection, five CBA and five Balb/C passageable mesothelioma cell lines have been produced and characterized, and these cells have similar growth factor and major histocompatibility complex (MHC) protein expression patterns to human mesothelioma cell lines. Animals with malignant mesothelioma demonstrate growth inhibition following therapy with interferon-α (INF-α) or interleukin-2 (IL-2) plus LAK cells. Clinical trials of immunotherapy in humans have commenced. Whereas therapy with intrapleural IL-2 plus LAK cells was associated with severe local and systemic side-effects and was therefore stopped, therapy with recombinant human interferon-alpha-2a (Roferon A) produced partial (>50%) reduction in tumour bulk in three out of 25 patients and a delayed complete response in another patient. Current trials utilize recombinant human interferon-alpha-2a plus adriamycin. We conclude that there is a solid scientific foundation for the establishment of investigative immunotherapeutic protocols for patients with malignant mesothelioma.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Conference Paper
Collection: School of Medicine Publications
 
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