Antigen Targets for the Development of Immunotherapies in Leukemia

Abstract

Immunotherapeutic approaches, including allogeneic stem cell transplantation and donor lymphocyte infusion, have significantly improved the prognosis of leukemia patients. Further efforts are now focusing on the development of immunotherapies that are able to target leukemic cells more specifically, comprising monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and dendritic cell- or peptide-based vaccination strategies. One main prerequisite for such antigen-specific approaches is the selection of suitable target structures on leukemic cells. In general, the targets for anti-cancer immunotherapies can be divided into two groups: (1) T-cell epitopes relying on the presentation of peptides via human leukocyte antigen (HLA) molecules and (2) surface structures, which are HLA-independently expressed on cancer cells. This review discusses the most promising tumor antigens as well as the underlying discovery and selection strategies for the development of anti-leukemia immunotherapies.

The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma

“…Jens Bauer 1,2,3 , Natalie Köhler 4,5 , Yacine Maringer 1,2,3 , Philip Bucher 3,6 , Tatjana Bilich 1,2,3 , Melissa Zwick 4,7 , Severin Dicks 7,8 , Annika Nelde 1,2,3 , Marissa Dubbelaar 1,2,3,9 , Jonas Scheid 1,2,9 , Marcel Wacker 1,2,3 , Jonas S. Heitmann 3,10 , Sarah Schroeder 1,2,11 , Jonas Rieth 1,2 , Monika Denk 1,2,12 , Marion Richter 1,2,12 , Reinhild Klein 13 , Irina Bonzheim 14 , Julia Luibrand 14 , Ursula Holzer 6 , Martin Ebinger 6 , Ines B. Brecht 6 , Michael Bitzer 3,12,15 , Article https://doi.org/10.1038/s41467-022-33746-3…”

“…One main problem for the development of antigen-specific immunotherapies is the lack of suitable target structures that show natural, highly frequent, and tumor-exclusive presentation on the cell surface of tumor cells and are recognized by the immune system 11 . Tumor antigens are represented by HLA-independent surface molecules or by HLA class I-and HLA class II-presented T cell epitopes, originating from intracellular proteins 12 . In terms of the latter, neoepitopes arising from tumor-specific mutations have been identified in recent years as the main specificity of anti-cancer T cell responses induced by ICIs, and were in turn suggested as prime candidates for T cell-based immunotherapy approaches [13][14][15] .…”

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

“…These highly promising target structures are represented by HLA-independent surface antigens, such as BCMA in MM. However, the number of such antigens is limited due to the required exclusive presentation on the surface of tumor cells 23 . HLA-dependent antigens, in contrast, can originate from any intracellular protein or domain and are not restricted to cell surface proteins.…”

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

“…The discovery and characterization of relevant transplantation antigens nonetheless hold great promise for the design of immunotherapies that could enhance the GVT effect and limit the occurrence of GVHD. The development of such immunotherapies depends on the identification of antigens that are specifically, or at least preferentially, expressed on hematopoietic and/or malignant cells (6,21). As such, Human leukocyte antigen (HLA) (the major histocompatibility antigens) and MiHA mismatches can be harnessed to treat hematological cancer patients.…”