HLA-A*24:02

Biochemical binding assays, molecular dynamics simulations, and structural and functional analyses demonstrate that high-affinity PC-CAR recognition of cross-reactive pHLAs necessitates the presentation of a specific peptide backbone, where subtle structural adaptations of the peptide are critical for high-affinity complex formation, and CAR T cell killing. Our results provide a molecular blueprint for engineering CARs with optimal recognition of tumor-associated antigens in the context of different HLAs, while minimizing cross-reactivity with self-epitopes.

Finally, we demonstrate potent and specific killing of neuroblastoma cells expressing these HLAs in vitro and complete tumour regression in mice. These data suggest that PC-CARs have the potential to expand the pool of immunotherapeutic targets to include non-immunogenic intracellular oncoproteins and allow targeting through additional HLA allotypes in a clinical setting.

P1, N=10, Recruiting, Lion TCR Pte. Ltd. | Trial completion date: Jul 2024 --> Jul 2028 | Trial primary completion date: Jul 2023 --> Jul 2026

CD8 T cells also showed Ki-67 expression and surrounded the CD8-negative tumor cells expressing Ki-67. These findings suggest that PBF TCR-T cell therapy might be a candidate immunotherapy for sarcoma highly expressing PBF.

Patients being HLA-A*02:01HLA-A*24:02 exhibited varying clinical outcomes, pointing to the presence of additional HLA-A alleles with potential prognostic value. Our data underline the HLA-A alleles as valuable prognostic biomarkers for PCa that may assist with the appropriate treatment and follow-up schedule based on the risk for disease progression to avoid over-diagnosis and over-treatment.

Further sequence and structure analyses also suggest that although the peptide loading complex would help with stabilizing the MHC molecule, the binding depends in a large part on the intrinsic affinity between the MHC molecule and the antigen peptide. Finally, our computational tools and analyses can be of great benefit to study the binding mechanism of different MHC types to their antigens, where it could also be useful in the development of higher affinity variant peptides and for personalized medicine.

P1/2, N=36, Recruiting, BriaCell Therapeutics Corporation | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

The study is ​a sub-study of the DOMEST (imatinib stop study), the DADI and first-line DADI trials (two dasatinib stop studies) approved by the institutional review board of each participating hospital ( UMIN000041798 ). Allelic polymorphisms of KIRs and HLAs can reflect NK cell immune response and can predict favorable achievement of TFR in CML. Chronic myeloid leukemia, Immunity, treatment-free remission, Tyrosine kinase inhibitor

B10 CAR-T cells could show specific cytotoxicity against RCC and osteosarcoma cells in vitro and in vivo. B10 CAR-T cells targeting the CSC/CIC antigen DNAJB8 might be a candidate immunotherapy for carcinoma and sarcoma.

P3, N=221, Completed, Sumitomo Pharma Oncology, Inc. | Active, not recruiting --> Completed

In conclusion, the biweekly WT1 Trio vaccine containing the WT1-332 helper T lymphocyte peptide induced more robust immune responses targeting WT1 than the weekly WT1-235 CTL peptide vaccine. Therefore, WT1-targeted immunotherapy may be a potential therapeutic strategy for rare cancers.

P1/2, N=36, Recruiting, BriaCell Therapeutics Corporation | Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Dec 2022 --> Jun 2023

P1/2, N=36, Recruiting, BriaCell Therapeutics Corporation | N=60 --> 36