Kelly E. Burgin

Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity.

Abstract. The use of fusions between dendritic cells (DCs) and tumor cells as vaccines has been proved very effective in stimulating antitumor immune responses, both in animal studies and in early human clinical trials. Because of the difficulty of purifying the hybrid cells from the fusion, fusion mixtures were used in these studies. Recently, we developed a technique using fluorescent-dye staining and fluorescence-activated cell sorting that enabled the hybrid cells to be instantly purified from the fusion mixture [10]. In the present study, the hybrid cells were purified from a fusion between mouse DCs and B16F0 melanoma tumor cells using the new technique. The purified cells, named instant dendritomas (IDs) were then compared with fusion mixtures in stimulating antitumor immune responses. The results from cytotoxicity assays, interferon-γ production and in vivo lung tumor metastasis demonstrated that IDs are more effective than fusion mixture in stimulating antitumor immunity. Meanwhile, there was no significant difference in the antitumor immunities activated by IDs from allogenic fusion or IDs from syngenic fusion.

Fusion protein from RGD peptide and Fc fragment of mouse immunoglobulin G inhibits angiogenesis in tumor.

Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The αvβ3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly-Asp) motif have high-binding affinity to the αvβ3 integrins in tumors. In this study, we designed a fusion protein containing the RGD sequence and the Fc fragment of mouse IgG in order to target the Fc portion of IgG to the tumor vasculature to elicit an antiangiogenesis immune response. In vivo angiogenesis and tumor studies demonstrated that the fusion protein (RGD/mFc) inhibited tumor angiogenesis and tumor growth and improved overall survival. This approach may generate new therapeutic agents for solid tumor treatment.

Synergistic anti‐tumor effect of glycosylphosphatidylinositol‐anchored IL‐2 and IL‐12

Preclinical and clinical studies have demonstrated that interleukin 2 (IL‐2), interleukin 12 (IL‐12), and some other cytokines, play important roles in activating host immune responses against tumor growth. However, severe side effects caused by systemic high‐dose administration of these cytokines limit their clinical application. In our previous study, local high doses of IL‐2 were achieved by a GPI‐anchoring technology; therefore, it will be interesting to know if this technology works for other cytokines.

Whole tumor cell vaccine with irradiated S180 cells as adjuvant

Whole tumor cell vaccines have been widely studied and remain promising cancer immunotherapies. In the present study, we discovered that vaccination with irradiated mouse sarcoma S180 tumor cells stimulated robust antitumor immunity to autologous tumor cells in both syngenic and allogenic mice. The antitumor activity requires both T and B cells, but not NK cells. When a mouse lung carcinoma (TC-1) whole tumor cell vaccine was combined with the S180 vaccine, the antitumor immunity against live TC-1 tumor cells is significantly enhanced compared to a TC-1 whole cell vaccine alone. This antitumor immunity not only prevents live tumor challenge but also eradicates existing tumor cells. A similar phenomenon was also observed when S180 vaccine was combined with LL2 Lewis lung carcinoma tumor cells. Therefore, S180 vaccine may serve as an adjuvant for other whole tumor cell vaccines.