H Haddada — Page 3 | Search PubMed

PubMedDate not supplied

[Natural cytotoxic activity in different experimental conditions in hamsters (author's transl)].

Lymphoid cells from normal hamsters from our inbred Z strain were evaluated for their natural cytotoxic activity against YAC cells (mouse lymphoma) and ZDc125 and EHB cells (cultured syngeneic hamster fibroblasts) employing the 51Cr-release cytotoxic essay. Natural cytotoxic reactivity was high in spleen, intermediate in peritoneal cells and very low in the thymus. Natural cytotoxic response was present in newborn animals, reaches a maximal level within 4-8 months and declines very slowly thereafter. Treatment of hamsters with a single dose of cyclophosphamide (Cy) augmented the natural cytotoxic reactivity 2 to 3 days after injection; this activity was suppressed thereafter and reappeared 20-25 days after the Cy injection. Growth of transplantable ZDc125 or EHB tumour in syngeneic hamsters inhibited the natural cytotoxic activity as soon as the tumour was palpable. Preincubation of target cells in sera of tumour-bearing animals diminished the level of natural cytotoxic activity of spleen lymphoid cells. One can postulate that this could be due to the presence of antibodies or immune complexes in those sera.

Aging↗

PubMedDate not supplied

Does preventive vaccination with engineered tumor cells work in cancer-prone transgenic mice?

The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice that express the SV40 large T and small t antigens under the control of hepatic antithrombin III (ASV-B)-regulatory sequences. These mice systematically develop hepatocarcinoma. Hepatoma cells, derived from ASV-B transgenic mice, were gene-transduced to express either interleukin-2, interleukin-4, the granulocyte-macrophage colony-stimulating factor, or the T-cell costimulatory molecule B7.1. First, we demonstrated the vaccine potential of engineered hepatoma cells by immunizing nontransgenic mice with these cells, which prevented the growth of subsequent grafted nontransduced hepatoma cells. However, vaccination of pretumoral transgenic animals with various combinations of engineered hepatoma cells failed to inhibit hepatoma onset and progression. Rather, tumor development in ASV-B mice appears to be dependent on the immune system, since neonatal induction of immunotolerance to tumor in ASV-B mice cells was associated with a moderate, but significant, acceleration of tumor development. These results seriously call into question the efficacy of this strategy of active vaccinotherapy against natural tumors.

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