Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies.

Cancer is one of the major global health burdens, and more effective treatments are needed. At present, there are surgery, targeted therapy, and immunotherapy for the treatment of tumors, but due to the limitations of diagnostic technology and drug resistance, surgery and targeted therapy have little effect. Active immunization in the field of immunotherapy can mobilize host immunity, trigger tumor-specific T-cell responses, and produce targeted cytotoxicity. Its efficacy largely depends on the targeted delivery efficiency of cancer vaccines. Although immunotherapy is more durable than other approaches, immunosuppression in the tumor microenvironment and immune evasion by malignant cells limit the therapeutic efficacy of cancer vaccines. To overcome these challenges, this review summarizes key strategies for improving vaccine vector targeting, as well as recent advances and trends in delivery systems.

Vaccinology has undergone a profound paradigm shift—from traditional empirical discovery to a rational, engineering-based discipline. This transformation is driven by the synergistic and iterative cycle between computational (in silico) prediction and rigorous experimental validation, now the cornerstone of modern, accelerated vaccine development. This review delineates the architecture of this integrated pipeline. We first survey the expanding computational toolbox for vaccine design, spanning immunoinformatics and reverse vaccinology for antigen discovery, AI-driven structure-based engineering of stabilized immunogens, and systems vaccinology for modeling immune dynamics. We then outline the “experimental gauntlet”: a hierarchy of biochemical, cellular, and in vivo preclinical assays that verify computational hypotheses—confirming molecular structures, binding kinetics, immunogenicity, and protective efficacy. The power of this fusion is exemplified by landmark case studies: the structure-guided triumph against Respiratory Syncytial Virus (RSV), the rapid development of COVID-19 mRNA vaccines, the iterative germline-targeting design of HIV immunogens, and the frontier of personalized neoantigen cancer vaccines. Together, these advances demonstrate that the union of predictive computation and empirical validation has moved from promise to proven paradigm. Looking ahead, emerging technologies such as generative AI and immune digital twins are poised to further accelerate this virtuous cycle, transforming vaccinology into a more precise, predictable, and rapid science capable of meeting future global health challenges.

Therapeutic vaccines are a key strategy to achieve the goal of “functional cure” of chronic viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human papillomavirus (HPV), and Epstein–Barr virus (EBV). Various platforms (such as viral vectors, nucleic acid vaccines, recombinant proteins, etc.) have successfully induced strong virus-specific T-cell responses in early trials, but their clinical efficacy is still limited by the immunosuppressive environment formed by the host. The core bottlenecks are severe T-cell exhaustion, viral immune escape, and various forms of local immune tolerance. Therefore, the field is moving toward combination therapies, including reduction of viral load, targeting of immune activation, and inhibition of inhibitory signaling pathways. This article summarizes the preclinical and clinical progress of therapeutic vaccines in the past decade, analyzes the major challenges in vaccine development, and discusses the future development directions in this field.

Triple-negative breast cancer (TNBC), characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is a highly aggressive molecular subtype with high recurrence and metastasis rates. Due to the absence of reliable molecular targets, surgery combined with chemotherapy remains the mainstay of clinical treatment. In recent years, immunotherapy has provided new strategies for TNBC management. Immune checkpoints are key regulatory molecules that maintain immune homeostasis, and blocking these checkpoints can restore T cell activity and enhance tumor cell killing. Immune checkpoint inhibitors (ICIs) have demonstrated clinical benefit, particularly in combination with chemotherapy for patients with locally advanced or metastatic TNBC. This review focuses on immune checkpoint–based immunotherapy in TNBC, providing an overview from mechanistic insights to clinical applications and emerging therapeutic strategies. In addition to ICIs, we discuss alternative approaches, such as bispecific antibodies, antibody–drug conjugates (ADCs), chimeric antigen receptor T cell (CAR-T) therapy, tumor vaccines, and oncolytic viruses (OVs), highlighting their current research progress and clinical applications in TNBC treatment.