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The spontaneous regression of neoplasms in mammals: possible mechanisms and their application in immunotherapy.

In mammalian cells, neoplastic transformation is directly associated with the expression of oncogenes, with the mutation, loss or simple inactivation of the function of tumor suppressor genes, and the production of certain growth factors. Genes for suppression of the development of the malignant immunophenotype, as well as inhibitory growth factors have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently observed in various cancers. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in the spontaneous regression (SR) of neoplasms. SR of neoplasms occurs when the malignant tumor mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic disease. This definition makes it clear that the term SR applies to neoplasms in which the malignant disease is not necessarily cured, and to cases where the regression may be neither complete nor permanent. A number of possible mechanisms of SR are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualized anticancer immunotherapy (biotherapy) is also discussed.

Animals↗
PubMed2002

Spontaneous regression of neoplasms: new possibilities for immunotherapy.

In mammalian cells, neoplastic transformation is directly associated with the expression of oncogenes, loss or simple inactivation of the function of tumour suppressor genes and the production of certain growth factors. Genes for suppression of the development of the neoplastic cellular immunophenotype, as well as inhibitory growth factors, have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently detected in various neoplasms. Telomerase activation is regarded as essential for cell immortalisation and its inhibition may result in spontaneous regression of neoplasms. This phenomenon of neoplasms occurs when the malignant tissue mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic growth. This definition makes it clear that the term 'spontaneous regression' applies to neoplasms in which the overall malignant disease is not necessarily cured and to cases where the regression may not be complete or permanent. A number of possible mechanisms of spontaneous regression are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualised and adequate antineoplastic immunotherapy (alternative biotherapy) is also discussed.

Animals↗
PubMed1976

Spontaneous tumor regression: possible relationship to in vitro parameters of tumor immunity.

Evidence is discussed from three animal systems (Shope papillomas in rabbits, Moloney sarcomas in mice, Schmidt-Ruppin-Rous sarcomas in Japanese quail) that immune reactions can be important in spontaneous tumor regression. In vitro studies performed in these systems indicate that blocking serum factors can thwart cell-mediated immune responses and that "unblocking" antibodies are often found in animals whose tumors have regressed. To what extent spontaneous regressions of human neoplasms are due to immunologic mechanisms is unknown; in 2 patients who had undergone spontaneous tumor regression, tumor cell cytotoxic lymphocytes and unblocking serum factors were detected. Better animal models and better knowledge about the mechanisms of tumor immune reactions are needed before tumor regression can be more successfully induced by immunologic manipulation (to what extent that will even be feasible in man is unknown).

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