Effective Tumor Vaccine Generated by Fusion of Hepatoma Cells with Activated B Cells

Abstract

Fusion of BERH-2 rat hepatocellular carcinoma cells with activated B cells produced hybrid cells that lost their tumorigenicity and became immunogenic. Syngeneic rats injected with BERH-2-B hybrid cells became resistant to challenge with parental BERH-2 cells, and rats with established BERH-2 hepatomas were cured by subsequent injection of BERH-2-B cells. Both CD4+ and CD8+ cells were essential for the induction of protective immunity; however, only CD8+ cells were required for the eradication of BERH-2 tumors. The generation of hybrid tumor cells that elicit antitumor immune responses may be a useful strategy for cancer immunotherapy.

T cell immunity using transgenic B lymphocytes

“…Possibly related to our system is the report on the immunogenicity of hepatoma cells fused with activated B lymphocytes (42), where the latter contribute costimulatory molecules (CD40 and CD86). In our case, B lymphocytes may be turned into APCs when CpG motifs in bacterial DNA signal TLR-9 intracellularly (43), even though spontaneous transgenesis does not induce cell-cycle entry and proliferation (unpublished data).…”

Hybrid cell vaccination for cancer immune therapy: First clinical trial with metastatic melanoma

“…A parallel trial with renal cell carcinoma has yielded similar results with respect to both the absence of severe side effects and initial indications of clinical responses (Kugler et al, 1998). The mechanisms of the therapeutic effects had been studied in animal models before (Stuhler and Walden, 1994;Guo et al, 1994) but needs to be analysed in humans as well. Although it was not the objective of the presented trial to study whether the conclusions drawn from the animal experiments apply to the situation in humans as well, histology done on metastasis that showed signs of regression provide evidence for vaccination induced mobilisation of helper and cytotoxic T cells and changes in the tumour environment mediated by these cells.…”

“…Mixtures of the tumour and antigen presenting cells were not effective (Stuhler and Walden, 1994;Guo et al, 1994). These anti-tumour effects were shown to be dependent on active collaboration of cytotoxic T cells, helper T cells and the antigen-presenting cells.…”

“…In all 3 studies, the animals were efficiently cured from the transplanted tumours and acquired a long-lasting immunity to subsequent challenges with the same tumour. In addition, these experiments have provided in vivo evidence for the epitope linkage requirement for helper T cell dependent CTL induction (Stuhler and Walden, 1994) as well as for the involvement of the B7/CD28 co-stimulatory pathway (Guo et al, 1994).…”

“…Combining these considerations, fusion of tumour cells and allo MHC class II bearing cells can render antigenic tumour cells immunogenic. The hybrid cells thus generated will display the full antigenicity of the tumour cell and be highly immunogenic by the effect of allogeneic MHC class II and co-stimulatory molecules contributed by the fusion partner cell (Chen et al, 1992;Guo et al, 1994). This concept has been tested in animal model experiments for thymoma (Stuhler and Walden, 1994), hepatocarcinoma (Guo et al, 1994) and adenocarcinoma (Gong et al, 1997).…”