CD30 and Peptide-MHC class I complexes presenting Epstein-Barr virus antigens (CD30/EBV-pMHC)

The target is a dual-antigen system comprising the CD30 receptor and peptide-MHC class I complexes presenting Epstein-Barr virus (EBV) antigens. CD30 (TNFRSF8) is a cell surface receptor and member of the tumor necrosis factor receptor superfamily that is highly and consistently expressed on the malignant Reed-Sternberg cells of Hodgkin lymphoma and certain non-Hodgkin lymphomas [2, 4]. Peptide-MHC class I complexes presenting EBV antigens are the natural targets of EBV-specific T cells (EBVSTs), which recognize these complexes via their endogenous T-cell receptors (TCRs) [1, 2]. This dual-targeting strategy is primarily employed in the development of CAR-modified EBVSTs, where the T cells are engineered to express a chimeric antigen receptor (CAR) specific for CD30 [1, 3]. The CAR component allows for direct, MHC-unrestricted recognition and killing of CD30-positive tumor cells, while the native TCR component provides additional costimulation and promotes long-term persistence through interactions with EBV-infected cells, such as B cells or EBV-positive tumor cells [2, 5]. This approach is particularly relevant for treating EBV-associated malignancies and aims to overcome limitations of conventional CAR-T therapies, such as poor persistence and tumor antigen escape [3, 4]. Clinical trials, such as NCT04288726 and NCT02917083, have explored this platform as an off-the-shelf therapy using allogeneic EBVSTs selected based on HLA matching to minimize graft-versus-host disease [3, 5]. The interaction with EBV-pMHC complexes can provide a vaccination-like effect, boosting the expansion and survival of the therapeutic T cells in vivo [1, 4]. Overall, this target combination represents a sophisticated approach to immunotherapy that leverages both synthetic and natural immune recognition mechanisms to enhance efficacy and safety [1, 2].

Other names

CD30TNFRSF8EBV-pMHCEpstein-Barr virus peptide-MHC complexCD30 and EBV-pMHCPeptide–MHC class I complexes presenting Epstein–Barr virus antigens and, in CAR-modified variants, CD30 on tumor cells

The mechanism of action involves dual targeting where the chimeric antigen receptor (CAR) provides MHC-unrestricted recognition of CD30 on tumor cells, while the native T-cell receptor (TCR) recognizes EBV-pMHC complexes, leading to enhanced T-cell activation, proliferation, and persistence.