Tumor cell control, cloned autologous cell transplantat in cancer, cell therapy in cancer, anti-oncogen transfer, transfection of healthy/repaired alleles, gene therapy in cancer
Approach to Tumor Cell
Control in Vivo
ENNO A. WINKLER
Medorganica (Cologne) 15 (1991), 114
Increasing numbers of studies are showing that formation of tumor cells is associated with mutational activation of cell integrated oncogenes (1,2). According to experimental and epidemiological data (3) these mutations might be caused by transcription errors or degeneration as well as biological, chemical and physical noxes. Several proceedings have been described how to functionally inactivate or substitute wildtype genes (4), unfortunately without gaining yet clinical relevance.
On the other hand there is clinical and laboratory evidence that healthy organisms and tissues are capable to control activated oncogenes and resulting tumor cells, and that in the case of clinical tumor growth the inhibitory or surveillance mechanisms must have failed. Recent reports indicate that tumor cell growth can be inhibited in culture and nude mice by influences of adjacent healthy cells and certain cellular proteins (5, 6) thus confirming clinical observations experienced by almost every oncologist. In early human breast cancer better tumor control is achieved by restricted surgery and radiation therapy than by radical mastectomy (7). This also seems to be true for tumors of the rectosigmoid (unpublished personal data).
Similar experiences are reported from radiation biology: Irradiated cells are better capable to repair DNA damage when imbedded in same type cells assembly.
Having these facts in mind - and being far away from already knowing in detail each molecular biologic step of tumor cell transformation and possibilities of correction - a new approach to tumor cell control or restoration of differentiation capability in primary tumors as well as in metastasis might be the intravenous/local intraarterial transplantation of autologous cells or in a further step the transfection of specific (antioncogenic) alleles, cloned from healthy parts of the primary tumor bearing tissue. It can be assumed that healthy cells or their fragments – like in bone marrow transplantation – only will adhere to mother tissue. Looking to the future even transfection of repaired or synthetic (8) dominant alleles or specific possibly omnihistocompatible fragments of alleles might become feasible.
Transferred to prior animal experiment and then to clinical oncology this would signify:
I Gross bulk tumor and metastasis surgery or radiation therapy in order to reduce tumor mass and secure intimate and quantitatively sufficient contact between remaining tumor cells and cloned autologous cells/alleles to be transplanted, preservation of tumor bed, preservation of organ.
II Cloning of healthy cells resected from the primary tumor bearing tissue.
III Post-operative/-radiation autotransplantation therapy.
- Bos, JL et al, Nature 327, 293-297 (1987)
- Liu, E et al, Nature 330, 186-188 (1987)
- Winkler, EA, Berliner Ärztekammer 21, 81-96 (1984)
- Herskowitz, I, Nature 329,219-222 (1987)
- Newmark, P, Nature 327, 101-102 (1987)
- Burck KB, Liu ET, Larrick JW: Oncogenes. Springer, Heidelberg 1988
- Fisher, B et al, N. Engl. J. Med. 312,665-673 (1985)
- Cumberlidge, G, Medical Focus (Würzburg), 1987, No. 4, 28-30
Dr. med. Enno A. Winkler
Instituto Nacional de Cancer