New perspectives in vaccines for cancer

The JAMA translational science review “Vaccines for Cancer” published in September 2026 examines the rapidly evolving role of vaccines in cancer prevention and treatment. After decades of limited therapeutic success, progress in tumour immunology, antigen discovery, genomic sequencing, and vaccine-delivery technologies has renewed interest in cancer vaccination. More than 2,000 immunogenic tumour-associated proteins or antigens have now been identified, and current strategies span broadly applicable shared-antigen vaccines through to fully individualized neoantigen vaccines. Cancer vaccines share three fundamental components: an antigen, an adjuvant that stimulates immune activation, and a delivery vehicle. Therapeutic vaccines aim to generate adaptive immunity by activating antigen-specific CD4+ and CD8+ T cells, as well as B cells. Antigen-presenting cells such as dendritic cells capture vaccine antigens, migrate to lymph nodes, and prime lymphocytes, which subsequently recognize and destroy antigen-expressing tumour cells. Unlike the rapid but short-lived innate response, adaptive immunity can be highly specific and durable. Preventive vaccination is already established for infection-associated malignancies. HPV vaccination reduces the risk of HPV-related cancers, while hepatitis B vaccination lowers hepatocellular carcinoma risk. However, because only about 13% of cancers have an infectious aetiology, most investigational cancer vaccines target tumour-derived cellular antigens rather than pathogens. Several immunologically mediated approaches are already approved for established cancer. Sipuleucel-T, an autologous cellular vaccine targeting prostatic acid phosphatase, improved overall survival in metastatic castrate-resistant prostate cancer; 36-month survival was 32% versus 23% with placebo (HR 0.78, 95% CI 0.61-0.98, p = 0.03), although progression time was not significantly improved. Talimogene laherparepvec (T-VEC), an intratumoral oncolytic herpes simplex virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), achieved a durable response rate of 16.3% versus 2.1% with GM-CSF in unresectable melanoma (16.3% [95%CI, 12.1%-20.5%] vs 2.1% [95%CI,0%-4.5%]; odds ratio, 8.9; p < .001) and generated evidence of systemic T-cell activation. Intravesical BCG (attenuated Mycobacterium bovis) remains an important immune-based treatment for high-risk non–muscle-invasive bladder cancer, while nadofaragene firadenovec, an intravesical adenoviral vector encoding interferon alfa-2b, is approved for BCG-unresponsive disease.