Development of Precision and Personalized Cancer Immunotherapy Using DNA Vaccines

Cancer immunotherapy has emerged as a promising approach for the treatment of human malignancies. The development of effective therapeutic cancer vaccines depends on the identification of appropriate tumor antigens and the induction of potent antigen-specific T-cell responses. DNA vaccines represent an attractive platform because of their simplicity, stability, favorable safety profile, and potential for rapid and cost-effective manufacturing. However, their relatively limited immunogenicity has historically presented a major challenge. Our research has focused on developing innovative strategies to enhance DNA vaccine potency, initially using human papillomavirus (HPV)-associated cancers as a model. The HPV16 E6 and E7 oncoproteins represent ideal tumor-specific antigens because of their essential roles in malignant transformation and continued expression in HPV-associated cancers. We have demonstrated that linking tumor antigens to calreticulin (CRT) enhances antigen processing and presentation through the MHC class I pathway, resulting in stronger antigen-specific CD8+ T-cell responses and improved antitumor activity. Furthermore, combining CRT-based DNA vaccine design with electroporation- mediated delivery substantially enhances vaccine potency. These advances have supported the clinical development of therapeutic HPV DNA vaccines for patients with HPV16-associated high-grade cervical intraepithelial neoplasia (CIN2/3). Importantly, the principles established through HPV vaccine development can be extended to other malignancies by targeting tumor-specific neoantigens. Two complementary approaches are being pursued: precision immunotherapy targeting shared (public) neoantigens and personalized immunotherapy targeting patient-specific neoantigens. For precision immunotherapy, we are developing DNA vaccines targeting oncogenic KRAS mutations, including G12D and G12V, which are frequently identified in pancreatic and other cancers. Using HLA transgenic mouse models, we have demonstrated that CRT-linked DNA vaccines targeting mutant RAS can induce mutation-specific CD8+ T-cell responses and antitumor effects, providing a rationale for further clinical development. In parallel, advances in tumor genomic sequencing and neoantigen identification have created opportunities to develop individualized DNA vaccines targeting patient-specific tumor mutations. The versatility of the DNA vaccine platform, together with enhanced delivery using electroporation, provides a promising strategy for translating these discoveries into personalized cancer immunotherapy. Collectively, our findings demonstrate how innovative DNA vaccine technologies developed for HPV-associated malignancies can serve as a foundation for precision and personalized immunotherapy against a broad spectrum of human cancers.

講者: Prof. T.-C. Wu, M.D., Ph.D. (Professor and Director of Gynecologic Pathology Professor of Oncology, Obstetrics & Gynecology, and Molecular Microbiology & Immunology, Johns Hopkins University Daniel Nathans Scholar Academician, Academia Sinica)

主持人: Dr. Pei-Wen Hsiao

時間:2026/12/28 11:00 AM

地點:農業科技大樓1樓A134演講廳