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Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
Genetic vaccination targeting T-cell receptors.
A P Godillot1, Q Fang, T Higgins
1Rheumatology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.
Methods in Molecular Medicine
|March 5, 2011
Summary
Cutaneous T-cell lymphomas (CTCL) are clonal diseases where malignant T cells express the T-cell antigen receptor (TCR). Clonal TCR-ß chain gene rearrangements confirm CTCL arises from a single malignant T cell clone.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- T-cell antigen receptor (TCR) genes rearrange during T-cell development, forming heterodimers on mature T-cells.
- TCRs provide antigen specificity in the context of major histocompatibility (MHC) molecules.
- Cutaneous T-cell lymphomas (CTCL) are a group of T-cell malignancies affecting the skin.
Purpose of the Study:
- To investigate the clonal nature of T-cell antigen receptor (TCR) gene rearrangements in cutaneous T-cell lymphomas (CTCL).
- To confirm that CTCL is a clonal disease originating from malignant T cells expressing the α/ß-TCR.
Main Methods:
- Analysis of T-cell antigen receptor (TCR) ß chain gene rearrangements.
- Examination of DNA samples from cutaneous tumors, peripheral blood lymphocytes, and lymph nodes of CTCL patients.
- Integration of findings with existing immunohistologic data.
Main Results:
- Clonal TCR-ß chain gene rearrangements were identified in DNA samples from CTCL patients.
- These rearrangements were found in tumors, peripheral blood, and lymph nodes.
- The presence of clonal rearrangements supports a monoclonal origin for CTCL.
Conclusions:
- CTCL is a clonal malignancy.
- Malignant T cells in CTCL express the α/ß-TCR.
- TCR gene rearrangement analysis is a valuable tool for diagnosing and understanding CTCL pathogenesis.
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