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Related Experiment Videos

Specific human cellular immunity to bcr-abl oncogene-derived peptides

M Bocchia1, T Korontsvit, Q Xu

  • 1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.

Blood
|May 1, 1996
PubMed
Summary

Researchers identified specific peptides from the bcr-abl fusion protein in chronic myelogenous leukemia (CML) that can trigger immune responses. This finding supports the development of peptide-based vaccines for CML treatment.

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Chronic myelogenous leukemia (CML) is driven by the t(9;22) translocation, producing P210 bcr-abl fusion proteins.
  • Unique junctional sequences in bcr-abl fusion proteins act as tumor-specific antigens.
  • Intracellular fusion proteins may be recognized by T lymphocytes via presented peptides.

Purpose of the Study:

  • To investigate the immunogenicity of CML-specific bcr-abl breakpoint peptides.
  • To determine if these peptides can elicit cytotoxic T lymphocyte (CTL) responses.
  • To assess the potential for peptide-based immunotherapy in CML.

Main Methods:

  • Synthesized peptides spanning the b3a2 CML breakpoint.
  • Tested peptide binding to HLA class I molecules (A3, A11, B8).

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  • Induced and assessed peptide-specific CTLs in HLA-matched donors.
  • Evaluated T-cell proliferation in response to a longer b3a2-25 peptide.

    • Main Results:

    • Four CML peptides bound with high/intermediate affinity to HLA-A3, A11, B8 molecules.
    • CML-A3/A11-peptide induced specific CTLs in 4/4 HLA-A3 donors, killing peptide-pulsed leukemia cells.
    • The peptide also induced killing of autologous/allogeneic PBMCs in 2/3 HLA-A3 donors.
    • Specific T-cell proliferation against the b3a2-25 peptide was observed in 3/7 donors (HLA-DR11).

    Conclusions:

    • Demonstrated the first evidence of a human cytolytic immune response against CML bcr-abl oncogene-derived peptides.
    • These findings provide a strong rationale for developing peptide-based vaccines for CML.