Patient-specific tumor-associated antigen and neoantigen presented by autologous dendritic cell (DC-presented TAA/Neoantigen)

Patient-specific tumor-associated antigens (TAAs) and neoantigens presented by autologous dendritic cells represent a personalized approach to cancer immunotherapy. TAAs are self-proteins that are overexpressed or aberrantly expressed in tumor cells, while neoantigens are unique, non-self proteins resulting from tumor-specific somatic mutations (Nature Reviews Cancer, https://www.nature.com/articles/s41568-019-0135-y). In this therapeutic strategy, a patient's own dendritic cells—the most potent antigen-presenting cells of the immune system—are isolated, matured, and loaded with these specific antigens ex vivo. Once re-infused, these dendritic cells migrate to the lymph nodes to present the antigens to naive T-cells, thereby inducing a robust and specific anti-tumor immune response (Journal of Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01032-2). This modality aims to overcome the immunosuppressive environment of the tumor and provide long-lasting immunological memory. It has been utilized in the development of therapies like Sipuleucel-T for prostate cancer and is being extensively studied in clinical trials for glioblastoma and melanoma (FDA, https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/provenge-sipuleucel-t). The specificity of neoantigens makes them particularly attractive targets as they minimize the risk of off-target toxicity compared to shared TAAs. However, the approach faces challenges including high manufacturing costs, logistical complexity, and the need for rapid production to match disease progression (Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2020.00688/full).

Other names

Personalized cancer vaccineDendritic cell vaccineAutologous dendritic cell immunotherapyTumor-specific antigen (TSA)NeoepitopeTumor-associated antigen (TAA)

Ex vivo loading of autologous dendritic cells with patient-specific antigens to induce a systemic, T-cell mediated anti-tumor immune response upon re-infusion (Nature Reviews Cancer, 2019).