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

• Main Authors: Alejandro Pando, John L. Reagan, Martha Nevola, Loren D. Fast
• Format: Article
• Language: English
• Published: BMC 2018-10-01
• Series: Experimental Hematology & Oncology
• Subjects: Leukemia; Alloreactivity; T cells; Cytolytic T lymphocytes; Immunotherapy; Cross-reactivity
• Online Access: http://link.springer.com/article/10.1186/s40164-018-0118-5

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.