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 with unmodified syngeneic tumor cells.


METHODS
Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2b) 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-2d) 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).


CONCLUSIONS
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.
Yu
Jin
J
Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA. yujin@musc.edu
Kindy
Mark S
MS
Gattoni-Celli
Sebastiano
S
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D004801:Eosine Yellowish-(YS); D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006416:Hematoxylin; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D013154:Spleen / Q000276:immunology
D019496:Cancer Vaccines; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin