(H-311) In situ formation of long-lasting tumor-specific T memory stem cells using nanoVax

Introduction:: Solid tumors account for more than 90% of cancer deaths, indicating the need for new and effective therapies. However, conventional treatments such as chemotherapy and radiation often cause harmful side effects, and cancer recurrence remains a significant problem. Personalized cancer immunotherapy, particularly cancer vaccines, offers a promising approach to preventing cancer recurrence by creating a long-term memory of immune cells against cancer. In this study, we developed a nanobiomaterial-based cancer vaccine (nanoVax) to deliver cancer neo-antigens and a cocktail of immune cell modulators to the tumor-draining lymph node, which can promote the formation of cancer-specific T memory stem cells (TMSCs) to help fight cancer.


Materials and Methods:: We synthesized hydrophobic-modified chitosan with palmitic acid and used a microfluidic platform to fabricate a series of nanoparticles with different sizes and surface charges. The nanoparticles were loaded with Poly(I:C) adjuvant, T cell modulator (TWS119), and either model tumor antigen (Ovalbumin peptide) or tumor lysates from murine melanoma (B16F10-Ova). We monitored and optimized the release of each ingredient and studied the effect of the designed particles on the activation and expansion of dendritic cells (DCs) and T cells in vitro and in vivo. We also used a murine model of melanoma to determine the protective effect of the developed cancer vaccine and tested whether our approach could form long-lasting memory T cells to prevent tumor recurrence.


Results, Conclusions, and Discussions:: We found that treatment with nanoVax significantly increased the activation of DCs (CD86+MHCII+CD11c+) compared to control samples. Moreover, nanoVax induced the formation of antigen-specific TMSCs (OVA+Sca-1+CD62L+CD44-CD8+CD3+) in vitro, and significantly shrank tumors in vivo following repeated injections (Fig. 1A). Treatment with nanoVax also supported the long-term survival of mice, with 30% of mice becoming tumor-free 100 days after treatment (Fig. 1B). Similar to in vitro observations, nanoVax can significantly affect the activation of DCs (Fig. 1C) and T cells (Fig. 1D) withing the tumor tissue as explored using flow cytometry.


Our study demonstrated that our nanoparticle vaccine's design could engineer in vivo formation of TMSCs, providing long-term immunity against primary tumors and preventing tumor recurrence. Our findings indicate that these immunomodulatory nanoparticles can interact effectively with immune cells in vitro and in vivo, presenting tumor neoantigens and adjuvant to activate antigen-presenting cells and promote the formation of cancer antigen-specific TMSCs.


Our engineered nanoparticles offer a promising platform for DC and T cell activation and in vivo clearance of tumors. Our approach lays the groundwork for the practical steps of translation toward personalized immunotherapy, potentially offering a new and effective therapy for cancer patients.


Acknowledgements (Optional): :

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