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Allogeneic and Autologous T cell Strategies to Enhance Targeting of Acute Myeloid Leukemias

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Targeted Therapy of Acute Myeloid Leukemia

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Acute myelogenous leukemia (AML) is a realistic target for T-cell immunotherapy because clinically powerful T-cell-mediated graft-versus leukemia (GVL) effects are well characterized following allogeneic stem cell transplantation (SCT). T-cell therapies in combination with SCT include donor lymphocyte infusions with or without added cytokines, infusions of selected T-cells deprived of graft-versus-host disease (GVHD) activity, and T-cells expressing a suicide gene permitting GVL but preventing GVHD by T-cell elimination. The identification of a series of minor histocompatibility antigens (mHAG) restricted to the myeloid lineage has made it possible to generate leukemia-reactive T-cells by expanding donor lymphocytes specific for a mHAG present in the recipient but absent in the donor. Key to the development of treatments that extend targeted T-cell strategies beyond SCT has been the identification of a range of leukemia-associated antigens (LAA). LAA can be used, either as inserts of the parent gene of a tumor antigen or as peptide mixes, to arm antigen-presenting cells (APCs). Dendritic cell APCs are used to induce LAA-specific T-cells either in vivo using the APCs as vaccines or in vitro generating LAA-specific T-cells in culture. Initial clinical results with mHAG-specific T-cells in transplanted patients show promising disease control but have identified off-target effects of some T-cell infusions, and reveal a tendency for tumor escape. Future developments for T-cell therapy for AML include the association of T-cell infusions with agents that can upregulate LAA, and the genetic modification of CTL to overcome tumor resistance.

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Authors and Affiliations

  1. Blood+Marrow Transplantation, Children’s National Health System, 111 Michigan Ave, NW, Suite 7225, 20010, Washington, DC, USA

    Catherine M. Bollard M.D.

  2. Stem Cell Allogenic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health P.O. Box 30105, 20892-1202, Bethesda, MD, USA

    Austin John Barrett M.D.

  3. University Children’s Hospital, Pediatric Hematology/Oncology, University of Wuerzburg, 1102 Bates Street, Suite 1770.01, 77030, Houston, TX, USA

    Gerrit Weber M.D.

Authors
  1. Gerrit Weber M.D.
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  2. Catherine M. Bollard M.D.
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  3. Austin John Barrett M.D.
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Corresponding author

Correspondence to Catherine M. Bollard M.D. .

Editor information

Editors and Affiliations

  1. Dept. Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Michael Andreeff

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© 2015 Springer-Verlag New York

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Weber, G., Bollard, C., Barrett, A. (2015). Allogeneic and Autologous T cell Strategies to Enhance Targeting of Acute Myeloid Leukemias. In: Andreeff, M. (eds) Targeted Therapy of Acute Myeloid Leukemia. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1393-0_41

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  • DOI: https://doi.org/10.1007/978-1-4939-1393-0_41

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