Induction of humoral and cellular anti-idiotypic immunity by intradermal injection of naked DNA encoding a human variable region gene sequence of an immunoglobulin heavy chain in a B cell malignancy

Abstract

The idiotypic determinants of a B cell neoplasia could provide a tumor-specific target for vaccinating patients against their B cell tumors. Several approaches for inducing idiotype-specific immunization have been reported, but their major theoretical focus was related to the induction of humoral immunity. We have investigated an immunization procedure with naked DNA encoding human variable region gene sequences of an immunoglobulin heavy chain (VH), which may generate both humoral and cellular immune responses against the idiotype of a B cell acute lymphoblastic leukemia (ALL). Using polymerase chain reaction (PCR) amplification, we investigated heavy chain variable region genes obtained from an ALL patient and whether they could induce humoral and cellular immune responses in DBA/2 mice. The VH sequence was cloned into a mammalian expression vector for intradermal DNA vaccination and into a bacterial expression vector to obtain VH protein for Western blotting. The mammalian expression vector encoding the VH gene was injected into mice three times at 7-day intervals and was transduced into P1HTR which is a syngeneic tumor of DBA/2, to serve as target cells to detect cellular immunity. Spleen cells from the inoculated mice exhibited a significant cytotoxic T lymphocyte response to the target cells. By Western blotting, we could also detect trace levels of anti-VH antibodies in all mice serum. This approach for the induction of cellular immunity by intradermal injection is easy and variable region-specific, and may be used as vaccines after chemotherapy treatment of B cell malignancies.