A novel costimulatory molecule gene-modified leukemia cell-derived exosome enhances the anti-leukemia efficacy of DC vaccine in mouse models.

Objectives: Leukemia cell-derived exosomes (LEXs), carrying leukemia cell-specific antigens, can serve as a source of antigen for dendritic cell (DC) vaccine loading. However, LEX-targeted DC-based vaccines have demonstrated limited antitumor immune effects in clinical trials, attributed to the low immunogenicity of LEXs and the scant levels of costimulatory molecules on DCs. The costimulatory molecules CD80 and CD86, which are crucial to DC function, play a significant role in enhancing immune efficacy. In this study, we explored the anti-leukemia immune response of costimulatory molecule gene-modified LEX-targeted DCs (LEX-8086) in vitro and in animal models.

Methods: DCs were incubated with LEX-8086 to produce LEX-8086-targeted DCs (DCs). ELISA, cytotoxicity assays and flow cytometry utilized to assess the antitumor efficacy of DCs in vitro. Flow cytometry was used to evaluate the immunomodulatory function of DCs in animal models.

Results: Our findings indicated that LEX-8086 enhanced the maturation and antigen-presenting ability of DCs. Immunization with DCs significantly activated CD8 T cells and boosted the CTL response in vitro. More importantly, DCs effectively suppressed tumor growth and exerted anti-leukemia effects in both prophylactic and therapeutic animal models. Furthermore, DCs promoted the proportion of CD4 T cells, CD8 T cells and M1 macrophages in the tumor environments both prophylactically and therapeutically. Treatment with DCs showed no significant difference in the levels of M2 macrophages but decreased the proportion of Tregs within the tumor bed during therapeutic experiments.

Conclusion: The results suggested that DCs induces a more effective anti-leukemia immunity compared to DCs in vivo and in vitro. DCs might achieve antitumor effects by elevating the numbers of CD4 T cells, CD8 T cells, and M1 macrophages in tumors. Our findings indicate that DCs could be leveraged to develop a new, highly effective vaccine for anti-leukemia immunity.