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CD45-derived peptide presented by HLA-A*01:01 (CD45/HLA-A*01:01)

Target
CD45/HLA-A*01:01
Molecular classification
Peptide-MHC complex, Antigen
01

Overview

CD45 (Protein Tyrosine Phosphatase Receptor Type C, or PTPRC) is a pan-hematopoietic transmembrane protein expressed on all nucleated cells of the hematopoietic system, where it plays a critical role in regulating T-cell and B-cell antigen receptor signaling. The target 'CD45-derived peptide presented by HLA-A*01:01' refers to a specific peptide fragment of the CD45 protein that is processed and displayed on the cell surface by the Human Leukocyte Antigen (HLA) allele A*01:01. This peptide-MHC (pMHC) complex serves as a highly specific target for adoptive T-cell therapies, particularly T-cell receptor-engineered T-cell (TCR-T) therapies designed to treat hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In clinical development, such as with TScan Therapeutics' TSC-102-A01, this target is utilized in the context of allogeneic hematopoietic cell transplantation (HCT). The therapeutic strategy involves engineering donor-derived T-cells with a TCR specific for the CD45/HLA-A*01:01 complex. When administered to a patient who is HLA-A*01:01 positive but has received a transplant from an HLA-A*01:01 negative donor, these engineered T-cells selectively eliminate the patient's remaining hematopoietic cells (including leukemic blasts) while sparing the donor-derived healthy blood system. This approach aims to prevent disease relapse and promote complete donor chimerism by exploiting the lineage-specific but HLA-restricted expression of the antigen.

Other names
PTPRC-derived peptide/HLA-A*01:01 complexCD45-A1 complexCD45-restricted HLA-A*01:01 antigenProtein tyrosine phosphatase receptor type C peptide/HLA-A*01:01
02

Mechanism of action

T-cell receptor-engineered T-cell (TCR-T) therapy

03

Biological functions

Immune recognitionT-cell activationAntigen presentation
04

Disease associations

Acute myeloid leukemiaMyelodysplastic syndromeAcute lymphoblastic leukemiaHematologic malignancy
05

Safety considerations

On-target off-tumor toxicity (if donor cells express HLA-A*01:01)Cytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)Graft-versus-host disease (GVHD)
06

Interacting drugs

TSC-102-A01
07

Biomarkers

HLA-A*01:01 expressionCD45 (PTPRC) expressionDonor chimerism

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