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  • Special Report
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Adoptive immunotherapy for myeloid malignancies

Leukemia Supplements volume 3, pages S21–S22 (2014)Cite this article

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In allogeneic stem cell transplantation (allo-SCT), much of the anti-tumor effect is derived from a graft versus tumor (GVT) response that is dependent on donor cell engraftment. In order to attain engraftment large doses of chemotherapy are administered to suppress the host’s immune system. Toxicities from allo-SCT are derived from these chemotherapy doses by causing myelosuppression and the resultant bleeding and infection risk that comes with it, as well as the threat that engrafted donor immune cells recognize normal rather than malignant cells, causing graft versus host disease (GVHD) rather than GVT. Previous work has shown the infusion of allogeneic matched and haploidentical peripheral blood stem cells with minimal conditioning can result in durable responses for patients with refractory leukemia/lymphoma in the absence of engraftment.1, 2, 3, 4 Furthermore, responders to therapy demonstrated a robust cytokine release syndrome that is similar to that seen in chimeric antigen receptor-modified T cells in its involvement of the release of interferon-γ (IFN-α) and interleukin-6 (IL-6).2, 5 Based on the loss of chimerism in responders, we hypothesize that the mechanism of action behind response is via the generation of a host versus tumor and not a graft versus tumor response.

Our current cellular therapy protocol seeks to further develop cellular infusion as a form of immunotherapy for refractory hematological malignancies.6 Patients are enrolled in an already FDA and institutional review board-approved trial that utilizes peripheral blood mononuclear cells (PBMNC) collected from human leukocyte antigen-haploidentical donors. The PBMNC are then infused unmanipulated and without any conditioning regimen to patients with refractory leukemia and lymphoma to create an allogeneic rejection effect that has previously been described in a mouse chimeric model.7, 8, 9, 10 We hypothesize that elimination of the conditioning regimen will decrease the likelihood of engraftment while increasing the host’s ability to generate an immunological response against the donor cells. The primary objective is the overall response rate, while secondary objectives seek to determine the underlying mechanism of action in terms of effector cell populations and how these effects can be further augmented.

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Acknowledgements

The symposium and publication of this supplement were sponsored by the Division of Hematology/Oncology at the Warren Alpert Medical School of Brown University and NIH Center of Biomedical Research Excellence (COBRE) for Stem Cells Biology at Rhode Island Hospital.

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  1. Division of Hematology/Oncology, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA

    J L Reagan

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Correspondence to J L Reagan.

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Reagan, J. Adoptive immunotherapy for myeloid malignancies. Leukemia Suppl 3 (Suppl 1), S21–S22 (2014). https://doi.org/10.1038/leusup.2014.12

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