Direct administration of human leucocyte antigen (dHLA) molecules into tumour sites: proposal for a new immunotherapy for cancer

Abstract

AbstractNatural elimination of cancer cells is mediated by human leucocyte antigen (HLA) Class I and II molecules [1] that bind to tumour protein fragments, move to the tumour cell surface and engage CD8+ lymphocytes for killing the tumour cell (HLA Class I) and CD4+ lymphocytes for antibody production against the tumour cell (HLA Class II). HLA Class I molecules are present in all nucleated cells, whereas Class II molecules are present only in antigen presenting cells, such as macrophages. These defence mechanisms are suppressed by tumour cells; this tumour-induced immunosuppression is partly reversed by immune checkpoint inhibitors (ICI), thus allowing the HLA-based tumour elimination to be active again; indeed, the success of ICI therapy partly depends on the HLA makeup of the recipient [2, 3]. Here, we propose a novel cancer immunotherapy consisting of administering the mRNA blueprints for the synthesis of specific HLA Class I molecules with high binding affinity and high immunogenicity to a tumour’s neoantigens. This should maximise the effectiveness of HLA-mediated tumour elimination.