Pre-chemotherapy tumor-derived nanovaccine fights multiple tumors in mice

A research team led by Professor 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 antigen-based nanovaccine derived from liposomal doxorubicin-treated tumor tissue. Effective in inducing strong immune defense against tumors. The study is published online in the journal Cell Reports Medicine.

Postoperative tumor recurrence and metastasis remain challenges in solid tumor surgery. The correlation between postoperative tumor recurrence and metastasis and host antitumor immune status is well established. Personalized cancer vaccines that use a patient’s own tumor as an antigen source stimulate a strong immune response and are effective in eliminating residual tumor foci after surgical intervention or targeting distant metastatic foci. , significantly reducing the risk of postoperative tumor recurrence. Metastasis.

The efficacy of autologous tumor cells in clinical trials is limited by poor immunogenicity. Tumor membranes contain tumor-presented and related antigens that can be developed to create personalized antigen libraries that more accurately reflect tumor antigen expression. Vaccines based on autologous tumor cell membrane antigens have been developed.

In clinical practice, patients receiving autologous tumor cell membrane vaccines (TMV) often have a history of previous therapeutic intervention, with chemotherapy being the main treatment. However, chemotherapy can alter the immunogenicity of tumor cell membranes, thereby affecting the therapeutic efficacy of TMV.

In this study, researchers used nanoformulated liposomal doxorubicin (NP-Dox) as a preoperative drug and investigated the effect of preoperative chemotherapy on TMV efficacy.

For the formulation of TMV, they obtained tumor membranes as antigens and combined resiquimod (R848), a potent dual Toll-like receptor 7/8 agonist with excellent efficacy, with poly(lactide-co-glycolic acid). ). PLGA) nanoparticles serve as adjuvants in vaccines.

TMV formulated from liposomal doxorubicin-treated tumors induces superior dendritic cell maturation and T cell activation compared to doxorubicin, preventing recurrence and metastasis in a postoperative mouse model, and post-operative It showed excellent efficacy in prolonging survival.

The researchers hypothesized that NP-Dox, as a typical inducer of immunogenic cell death in tumors, upregulates the expression of immune-related molecules on tumor cell membranes and enhances the immunogenicity of tumor membrane antigens. has been demonstrated. Furthermore, they showed that NP-Dox improved the immunological status of the tumor microenvironment and created favorable conditions for subsequent nanovaccine immunization.

“In previous studies, we developed an integrated vaccine formulation based on autologous tumor membrane antigens and bacterial cell membrane adjuvants, which could achieve enhanced anti-tumor immune responses with a good biosafety profile. ” said the doctor. Professor Zhao Ruifang of NCNST and lead author of the study.

“However, in terms of clinical applications, we found that patients received a variety of treatments before using autologous tumor membrane vaccines, with chemotherapy being relatively common.”

“This study provides valuable insight into the clinical application of TMV and demonstrates the potential of TMV in solid tumor treatment. At the same time, this study uses nanodrugs both preoperatively and postoperatively to “This study demonstrates the advantages of nanotechnology in the integrated application of adjuvant chemotherapy and tumor immunotherapy,” said Professor Nie Guangjun from NCNST, the study’s other lead author.