Patient-specific neoantigen–Major Histocompatibility Complex on autologous dendritic cells (NeoAg-MHC-DC)

Patient-specific neoantigen–MHC complexes on autologous dendritic cells represent a highly personalized form of cancer immunotherapy. This approach involves identifying unique somatic mutations (neoantigens) from a patient's tumor through genomic sequencing and then loading these antigens onto the patient's own harvested dendritic cells (Hu et al., 2021). These dendritic cells process the neoantigens and present them via Major Histocompatibility Complex (MHC) molecules, effectively acting as a blueprint for the immune system to recognize the cancer (Schumacher & Schreiber, 2015). Once re-infused, these cells migrate to the lymph nodes where they activate and expand a population of neoantigen-specific T-cells (Ott et al., 2017). These T-cells then circulate throughout the body to specifically target and eliminate tumor cells that express the corresponding mutated proteins. Because neoantigens are absent in healthy tissues, this strategy minimizes off-target toxicity while maximizing the precision of the anti-tumor response (Sahin et al., 2017). This modality is currently being evaluated in clinical trials for various solid tumors, often in combination with immune checkpoint inhibitors to enhance the durability of the immune response (Ding et al., 2023).

Other names

Personalized neoantigen-pulsed dendritic cellsAutologous neoantigen-loaded dendritic cellsNeoantigen-MHC complexTumor-specific neoantigen-presenting dendritic cells

Dendritic cells (DCs) are loaded with patient-specific neoantigens (mutated peptides or mRNA), which are processed and presented on MHC Class I and II molecules (Hu et al., 2021). These DCs then migrate to lymph nodes to prime and activate neoantigen-specific CD8+ and CD4+ T cells, which subsequently infiltrate the tumor and induce cell death (Ott et al., 2017).