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Synthetic tumor-specific breakpoint peptide vaccine in patients with chronic myeloid leukemia and minimal residual disease

A Phase 2 Trial

  1. Nitin Jain MD1,
  2. James M. Reuben PhD2,
  3. Hagop Kantarjian MD1,
  4. Changping Li MD2,
  5. Hui Gao PhD2,
  6. Bang-Ning Lee PhD2,
  7. Evan N. Cohen BS2,
  8. Theresa Ebarb RN1,
  9. David A. Scheinberg MD, PhD3,
  10. Jorge Cortes MD1,†,*

Article first published online: 17 JUN 2009

DOI: 10.1002/cncr.24468

Issue

Cancer

Cancer

Volume 115, Issue 17, pages 3924–3934, 1 September 2009

Additional Information

How to Cite

Jain, N., Reuben, J. M., Kantarjian, H., Li, C., Gao, H., Lee, B.-N., Cohen, E. N., Ebarb, T., Scheinberg, D. A. and Cortes, J. (2009), Synthetic tumor-specific breakpoint peptide vaccine in patients with chronic myeloid leukemia and minimal residual disease. Cancer, 115: 3924–3934. doi: 10.1002/cncr.24468

Author Information

  1. 1

    Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

  2. 2

    Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

  3. 3

    Molecular Pharmacology and Chemistry Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, New York

  1. †

    Fax: (713) 794-4297

*Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030

Publication History

  1. Issue published online: 20 AUG 2009
  2. Article first published online: 17 JUN 2009
  3. Manuscript Accepted: 3 FEB 2009
  4. Manuscript Revised: 29 JAN 2009
  5. Manuscript Received: 16 DEC 2008

Funded by

  • National Institute of Health. Grant Number: PO1 CA23766

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Keywords:

  • peptide;
  • vaccine;
  • tyrosine kinase inhibitor;
  • imatinib;
  • chronic myeloid leukemia

The use of heteroclitic peptides in chronic myelogenous leukemia may contribute to disruption in immune tolerance. In this study, 3 of 10 patients achieved a 1-log reduction in Bcr-Abl transcript levels.

Abstract

BACKGROUND:

Imatinib is the current standard frontline therapy for chronic myelogenous leukemia (CML). In the majority of patients, imatinib induces a complete cytogenetic response (CCyR); however, complete molecular responses are infrequent. The Bcr-Abl fusion creates a unique sequence of amino acids that could constitute a target for immunomodulation.

METHODS:

A mixture of heteroclitic and native peptides derived from both b3a2 and b2a2 sequences was used to vaccinate patients with CML in CCyR who were receiving imatinib therapy and who had stable Bcr-Abl transcript levels.

RESULTS:

Ten patients were enrolled, all with b2a2 transcripts (including 2 patients who had coexpression of b2a2 and b3a2). Patients had received imatinib for a median of 62 months. Three of 10 patients achieved 1-log reduction in Bcr-Abl transcript levels, including the 2 patients who had received previous interferon therapy, and 3 other patients achieved a major molecular response. The vaccine was tolerated well, and there were no grade ≥3 adverse events. Vaccination did not affect the leukocyte profiles in peripheral blood except for regulatory T cells, which were down-regulated briefly during the late stage of vaccination in patients who achieved approximately 1-log reduction in Bcr-Abl transcript levels.

CONCLUSIONS:

The current data suggested that vaccination-related transient disruption of immune tolerance may contribute to the reduction in Bcr-Abl transcripts. Clinically, this Bcr-Abl peptide vaccine may transiently improve the molecular response in a subset of patients with CML. Cancer 2009. © 2009 American Cancer Society.

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