Improved Therapeutic Outcome Following Combination Immunogene Vaccination Therapy in Murine Myeloma

Abstract

Increasing evidence suggests a role for immunologic vaccination and therapy in the management of minimal residual myeloma. We have previously demonstrated a synergistic effect of combining the Th1 stimulating cytokine IL-12 with the co-stimulatory molecule CD80 in murine myeloma vaccination therapy. We reasoned that the efficacy of such treatment might be further improved by incorporating additional gene products which enhance the function of antigen presenting cells. Studies were therefore conducted with murine myeloma BM1 cells expressing Flt3L (membrane bound or soluble forms) or GM-CSF and the IL-12 x CD80 combination. Single agent and combined therapeutic approaches were explored. All gene-modified BM1 cells, except BM1/IL-12 x CD80, developed tumors when subcutaneously injected into BALB/c mice. As prophylactic tumor vaccines, the combined use of gene-modified BM1/sFlt3L+GM-CSF+IL-12 x CD80 was most effective, providing 100% protection against subsequent parental BM1 tumor challenge. By comparison, only partial protection was observed with any single gene-engineered tumor vaccine. Notably, IL-12 x CD80 coexpressing BM1 cell vaccines were the most effective therapeutic vaccine in a minimal disease model. Such protective vaccination was achieved by stimulation of lymphocyte proliferation and enhancement of cytotoxic lymphocyte activity.

Increased risk of cancer in chronic dialysis patients: a population-based cohort study in Taiwan

“…Our study showed that the highest SIR of cancer in chronic dialysis patients was that for bladder cancer (SIR: 8.2, 95% CI: 6.7-9.9) compared to that in their healthy counterparts. This is different from the international collaborative studies [6,14,24] which found that kidney cancer had the highest SIR of cancers in chronic dialysis patients. The reason for this discrepancy is unknown, but it may be associated with the heavy consumption of some Chinese herbal products or compound analgesics in the Taiwanese population [22,25].…”

Gene therapy for hematological malignancies

“…Li et al [78] investigated vaccines consisting of a retroviral-transduced myeloma cell line (B9BM1) expressing single or combinations of transgenes (GM-CSF, IL-12, CD80, Flt3L) in a mouse model. They demonstrated that the combined use of GM-CSF, IL-12, CD80 is superior to the use of any single gene product in the protection against subcutaneous challenge with parental tumor cells.…”

Immunomodulatory gene therapy for haematological malignancies

“…Li et al (1999) investigated vaccines consisting of a retroviral transduced myeloma cell line (B9BM1) expressing single or combinations of transgenes (GM‐CSF, IL‐12, CD80, Flt3L) in a mouse model. They demonstrated that the combined use of GM‐CSF, IL‐12 and CD80 is superior to the use of any single gene product in the protection of s.c. challenge with parental tumour cells.…”