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Semi-allogeneic vaccine for T-cell lymphoma

BACKGROUND: Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge wit...

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Detalles Bibliográficos
Autores principales: Yu, Jin, Kindy, Mark S, Gattoni-Celli, Sebastiano
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971246/
https://www.ncbi.nlm.nih.gov/pubmed/17686178
http://dx.doi.org/10.1186/1479-5876-5-39
Descripción
Sumario:BACKGROUND: Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells. METHODS: Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2(b)) and BALB/c-derived renal adenocarcinoma RAG cells (H-2(d)). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2(b)) before challenging the mice with a tumorigenic dose of EL-4 cells. RESULTS: Semi-allogeneic tumor cell hybrids could not form a tumor in the animal host because they expressed allogeneic determinants (H-2(d)) and were rejected as a transplant. However, they conferred protection against a tumorigenic challenge of EL-4 cells compared to control mice that were mock-vaccinated with i.p.-injected phosphate-buffered saline (PBS) and in which EL-4 lymphomas grew rapidly to a large size in the peritoneal cavity. Screening of spleen-derived RNA by means of focused microarray technology revealed up-regulation of genes involved in the Th-1-type immune response and in the activation of dendritic antigen-presenting cells (APC). CONCLUSION: The results of our studies are entirely consistent with the concept that CD80- and CD86-expressing APC play a central role in mediating the immune protection induced by semi-allogeneic vaccines by activating a Th-1 response and instructing T cells responsible for killing autologous tumor cells.