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Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia

Abstract

Although the immune system has long been implicated in the control of cancer, evidence for specific and efficacious immune responses in human cancer has been lacking. In the case of chronic myelogenous leukemia (CML), either allogeneic bone marrow transplant (BMT) or interferon-α2b (IFN-α2b) therapy can result in complete remission, but the mechanism for prolonged disease control is unknown and may involve immune anti-leukemic responses. We previously demonstrated that PR1, a peptide derived from proteinase 3, is a potential target for CML-specific T cells. Here we studied 38 CML patients treated with allogeneic BMT, IFN- α2b or chemotherapy to look for PR1-specific T cells using PR1/HLA-A*0201 tetrameric complexes. There was a strong correlation between the presence of PR1-specific T cells and clinical responses after IFN-α and allogeneic BMT. This provides for the first time direct evidence of a role for T-cell immunity in clearing malignant cells.

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Figure 1: PR1/HLA-A2 tetramer+ CTL are found only in PBMC from CML patients.
Figure 2: Longitudinal follow-up of 6 CML patients using the PR1/HLA-A2 tetramer.
Figure 3: Patient PBMC containing PR1-specific CTL & pp65-specific CTL specifically lyse peptide-coated target T2 cells.
Figure 4: PBMC taken from DLI recipient UPN 25 lyse recipient marrow leukemia cells, but not normal donor marrow cells.
Figure 5: PBMC from DLI recipient UPN 25 lyse HLA-A2.1+ CML cells, but not HLA-2.1- CML cells or HLA-A2.1+ healthy donor marrow cells.

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Acknowledgements

We thank the HLA laboratory at the M. D. Anderson Cancer Center for performing HLA testing of all patients, donors and healthy volunteers. Supported by grants from the Leukemia Society of America (LSA 6148-99 to J.J.M.), the U.S. Public Health Service (CA81247 to J.J.M., AI22511 to M.M.D.), and the Howard Hughes Medical Institute (to M.M.D.). P. P. Lee is supported by a physician scientist award from the National Institutes of Health (CA72976).

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Correspondence to Jeffrey J. Molldrem.

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Molldrem, J., Lee, P., Wang, C. et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 6, 1018–1023 (2000). https://doi.org/10.1038/79526

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