A research team led by Prof. NIE Guangjun from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) and collaborators have demonstrated a tumor membrane antigens-based nanovaccine derived from liposomal doxorubicin treated tumor tissues, which is efficacious in inducing a potent immunological defense against tumors. The study was published online in Cell Reports Medicine.
Surgery continues to be the primary treatment modality for the majority of solid tumors; however, the challenges of postoperative tumor recurrence and metastasis persist. The correlation between postoperative tumor recurrence and metastasis and the host's antitumor immune status is well-established. Personalized cancer vaccines, using the patient's own tumor as an antigen source, stimulate a robust immune response that is efficacious not only in eliminating residual neoplastic foci following surgical intervention but also in targeting metastatic lesions at a distance, significantly reducing the risk of postoperative tumor recurrence and metastasis.
Although autologous tumor cells cover the comprehensive and personalized antigen repertoire, their efficacy in clinical trials has been limited by their weak immunogenicity. The tumor membrane contains tumor-presented antigens and associated antigens, which can be developed into a personalized antigen library that more accurately reflects the expression of tumor antigens. Consequently, vaccines based on autologous tumor cell membrane antigens have been developed. However, within the realm of clinical practice, patients who are administered autologous tumor cell membrane-based vaccines (TMVs) frequently have a history of prior therapeutic interventions, with chemotherapy being the predominant modality. However, chemotherapy has the potential to alter the immunogenic properties of tumor cell membranes, consequently impacting the therapeutic efficacy of the TMVs.
In this study, the researchers investigated the effects of preoperative chemotherapy on the efficacy of TMVs, employing nano-formulated liposomal doxorubicin (NP-Dox) as a preoperative medication. For the formulation of the TMVs, they obtained the tumor membrane as the antigen, and resiquimod (R848), a potent dual Toll-like receptor 7/8 agonist with excellent efficacy, was encapsulated in Poly (lactide-co-glycolic acid) (PLGA) nanoparticles to act as the adjuvant of the vaccine. The TMVs formulated from liposomal doxorubicin-treated tumors induce superior dendritic cell maturation and T cell activation compared to doxorubicin, thus demonstrating better efficacy in preventing recurrence and metastasis in the postoperative murine model, as well as in extending postoperative survival.
Mechanistically, researchers demonstrated that NP-Dox, as a paradigmatic inducer of immunogenic cell death in tumors, upregulates the expression of immune-related molecules on the tumor cell membrane, thereby enhancing the immunogenicity of tumor membrane antigens. Moreover, NP-Dox also improves the immunological status of the tumor microenvironment, thus creating favorable conditions for subsequent nanovaccine immunization.
“This study can also be considered as a supplement to our previous work. In our previous study, we developed an integrated vaccine formulation based on autologous tumor membrane antigens and bacterial cytoplasmic membrane adjuvants, which could achieve enhanced antitumor immune responses with a favorable biosafety profile. Based on its excellent efficacy, we are vigorously advancing its transition to clinical applications” says ZHAO Ruifang, an Associate Professor of NCNST and the lead author of the current work. “However, in clinical practice, we found that patients had undergone various treatments before using autologous tumor membrane vaccines, with chemotherapy being relatively common. Therefore, we conducted this study and were pleasantly surprised to find that the efficacy of autologous tumor membrane nanovaccines is enhanced when administered after preoperative liposomal doxorubicin chemotherapy.”
“This study provides valuable insights into the clinical utilization of TMVs, demonstrating substantial potential in solid tumor treatments. Concurrently, we employ nano-drugs both pre-and postoperatively in this study, fully showcasing the superiority of nanotechnology in the combined application of neoadjuvant chemotherapy and tumor immunotherapy.” NIE Guangjun says, a Professor of NCNST and the senior author of the current work.
Schematic representation of nanotechnology's dual role in enhancing personalized tumor vaccine therapy in conjunction with neoadjuvant chemotherapy(Image by NIE Guangjun et al)
Contact: NIE Guangjun
National Center for Nanoscience and Technology (NCNST)
E-mail: niegj@nanoctr.cn
