Alloantigen gene therapy for head and neck cancer: evaluation of animal models.
BACKGROUND
Human trials of alloantigen gene therapy, using the class I major histocompatibility complex (MHC) HLA-B7, have demonstrated the potential efficacy of this treatment for head and neck cancer. Its mechanism remains unclear. An immune-competent mouse model of MHC gene therapy to test factors potentially important to the tumor response is needed.


METHODS
Two cell lines were used, B4B8 cells that grow in Balb/c mice and SCC-VII cells that grow in C3H mice. The mouse MHC H2-K(b) was used as the therapeutic gene, because it is an alloantigen to both mice strains. Plasmids that encode the H2-K(b) cDNA were prepared, and the cell lines were transfected. Mice were injected subcutaneously with naive cells to determine the tumor kinetics and serve as controls. Mice were injected with H2-K(b) transfected cells and tumor growth was compared with controls. Mice that did not grow tumor were rechallenged with naive cells to assess for tumor immunity. Mice were injected with transfected and naive cells admixed to determine whether the concentration of the alloantigen is important.


RESULTS
B4B8 tumors grew slowly, whereas SCC-VII tumors grew rapidly. Transfection with H2-K(b) plasmid prevented or inhibited tumor growth of both the B4B8 and SCC-VII tumors. This growth inhibition was independent of the number of cells injected. In the mice that did not grow tumor, tumor immunity was demonstrated after challenge with naive cells in both models. There was no relationship between induction of immunity and the timing of the challenge or initial cell quantity. The mice injected with a mixture of naive and transfected cells grew tumor, although growth was delayed in the B4B8 model.


CONCLUSIONS
The results demonstrate that the two mouse models can serve as a rapid and slow growing tumor model of alloantigen gene therapy. In addition, it was noted that initial tumor cell number is not a significant factor for predicting tumor response and demonstrated that in both of these models alloantigen gene therapy results in significant antitumor immunity.
Gleich
Lyon L
LL
Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati Medical Center, P.O. Box 670528, 213 Albert Sabin Way, Cincinnati, Ohio 45267-0528, USA. lyon.gleich@uc.edu
Li
Ya-Qin
YQ
Li
Shunan
S
Gluckman
Jack L
JL
Stambrook
Peter J
PJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D015316:Genetic Therapy; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D066298:In Vitro Techniques; D007519:Isoantigens / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D007519:Isoantigens