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Exp Hematol Oncol. 2018 Oct 4;7:25. doi: 10.1186/s40164-018-0118-5. eCollection 2018.

Induction of anti-leukemic responses by stimulation of leukemic CD3+ cells with allogeneic stimulator cells.

Author information

1
Division of Hematology/Oncology, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, One Hoppin Street, Coro West Suite 5.0.1, Providence, RI 02903 USA.

Abstract

Background:

Immunotherapeutic protocols have focused on identification of stimuli that induce effective anti-leukemic immune responses. One potent immune stimulus is the encounter with allogeneic cells. Our group previously showed that the infusion of haploidentical donor white blood cells (1-2 × 108 CD3+ cells/kg) into patients with refractory hematological malignancies induced responses of varying magnitude in over half of the patients. Because donor cells were eliminated within 2 weeks in these patients, it is presumed that the responses of recipient lymphocytes were critically important in achieving prolonged anti-leukemic responses.

Methods:

The role of patient CD3+ cells in anti-leukemic responses was examined by isolating peripheral blood mononuclear cells from newly diagnosed leukemic patients. Immunophenotyping was performed on these peripheral blood mononuclear cells. CD3+ cells were isolated from the peripheral blood mononuclear cells and tested for their ability to proliferate and lyse autologous leukemic cells when stimulated with unrelated allogeneic cells.

Results:

Allostimulated CD3+ cells effectively generated cytolytic responses to autologous CD3-cells in 11/21 patients. Increased numbers of CD4+ cells expressing high levels of granzyme A, B and perforin and CD8+CD39+ cells were found in nonresponsive CD3+ cells.

Conclusions:

These results indicate that CD3+ cells from leukemic patients are capable of generating anti-leukemic responses when stimulated with unrelated allogeneic cells. This model can be used to identify approaches using alloreactive responses by patient lymphocytes to enhance in vivo anti-leukemic responses.

KEYWORDS:

Alloreactivity; Cross-reactivity; Cytolytic T lymphocytes; Immunotherapy; Leukemia; T cells

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