Basic study of polynucleotide vaccine for tumor immunotherapy

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[PURPOSE] Intramuscular injection of naked DNA such as plasmid-type expression vector leads to the expression of coded protein in the muscle, and host immune response against the protein is elicited when it is non-self like viral protein. In present study we investigate whether this new method is applicable to cancer immunotherapy or not. [METHOD] At first several kinds of CAT expression vectors were intramusculary injected to perform CAT assay with muscular extract and CAG promoter and CE promoter were found to be most efficient in muscle. cDNA designated as H52, which codes one of melanoma antigens expressed on murine melanoma cell line B16. was inserted downstreams of CAG promoter (pCAGH52). Another cDNA, which codes mutant p53 protein expressed in murine fibrosarcoma cell line Meth-A, was inserted downstreams of CE promoter (pCEp53). C57BL or BALB/c mice were intramusculary injected thrice at one week interval with 100 microgram of pCAGH52 or pCEp53 respectively. One week after the last injection those mice were injected subcutaneously with 100000 cells of B16 or Meth-A respectively. [RESULT] There was no difference in tumor incidence between treated group and control group and survival was not prolonged by DNA injection. [CONCLUSION] Simple DNA injection is not sufficient to elicit host immune response against autologous tumor. Becausae the amount of protein produced after DNA injection is very small, some adjuvant would be necessary to be recognized by antigen presenting cells.