TY - JOUR
T1 - Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation
AU - Laport, Ginna G.
AU - Sheehan, Kevin
AU - Baker, Jeanette
AU - Armstrong, Randall
AU - Wong, Ruby M.
AU - Lowsky, Robert
AU - Johnston, Laura J.
AU - Shizuru, Judith A.
AU - Miklos, David
AU - Arai, Sally
AU - Benjamin, Jonathan E.
AU - Weng, Wen Kai
AU - Negrin, Robert S.
N1 - Funding Information:
Financial disclosure: This work was supported in part by National Institutes of Health Grant PO1 CA049605 .
PY - 2011/11
Y1 - 2011/11
N2 - Donor leukocyte infusions induce remissions in some patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT); however, graft-versus-host disease (GVHD) remains the major complication of this strategy. Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes that express the CD3 +CD56 + phenotype and show marked up-regulation of the natural killer cell receptor NKG2D (CD314). CIK cells are non-major histocompatibility complex-restricted and NKG2D-dependent in target recognition and cytotoxicity. We explored the feasibility of ex vivo expansion of allogeneic CIK cells in patients with relapsed hematologic malignancies after allogeneic HCT. Eighteen patients (median age, 53 years; range, 20-69 years) received CIK cell infusions at escalating doses of 1 × 10 7 CD3 + cells/kg (n = 4), 5 × 10 7 CD3 + cells/kg (n = 6), and 1 × 10 8 CD3 + cells/kg (n = 8). The median expansion of CD3 + cells was 12-fold (range, 4- to 91-fold). CD3 +CD56 + cells represented a median of 11% (range, 4%-44%) of the harvested cells, with a median 31-fold (range, 7- to 515-fold) expansion. Median CD3 +CD314 + cell expression was 53% (range, 32%-78%) of harvested cells. Significant cytotoxicity was demonstrated in vitro against a panel of human tumor cell lines. Acute GVHD grade I-II was seen in 2 patients, and 1 patient had limited chronic GVHD. After a median follow-up of 20 months (range, 1-69 months) from CIK infusion, the median overall survival was 28 months, and the median event-free survival was 4 months. All deaths were due to relapsed disease; however, 5 patients had longer remissions after infusion of CIK cells than from allogeneic HCT to relapse. Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD, supporting further investigation as an upfront modality to enhance graft-versus-tumor responses in high-risk patient populations.
AB - Donor leukocyte infusions induce remissions in some patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT); however, graft-versus-host disease (GVHD) remains the major complication of this strategy. Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes that express the CD3 +CD56 + phenotype and show marked up-regulation of the natural killer cell receptor NKG2D (CD314). CIK cells are non-major histocompatibility complex-restricted and NKG2D-dependent in target recognition and cytotoxicity. We explored the feasibility of ex vivo expansion of allogeneic CIK cells in patients with relapsed hematologic malignancies after allogeneic HCT. Eighteen patients (median age, 53 years; range, 20-69 years) received CIK cell infusions at escalating doses of 1 × 10 7 CD3 + cells/kg (n = 4), 5 × 10 7 CD3 + cells/kg (n = 6), and 1 × 10 8 CD3 + cells/kg (n = 8). The median expansion of CD3 + cells was 12-fold (range, 4- to 91-fold). CD3 +CD56 + cells represented a median of 11% (range, 4%-44%) of the harvested cells, with a median 31-fold (range, 7- to 515-fold) expansion. Median CD3 +CD314 + cell expression was 53% (range, 32%-78%) of harvested cells. Significant cytotoxicity was demonstrated in vitro against a panel of human tumor cell lines. Acute GVHD grade I-II was seen in 2 patients, and 1 patient had limited chronic GVHD. After a median follow-up of 20 months (range, 1-69 months) from CIK infusion, the median overall survival was 28 months, and the median event-free survival was 4 months. All deaths were due to relapsed disease; however, 5 patients had longer remissions after infusion of CIK cells than from allogeneic HCT to relapse. Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD, supporting further investigation as an upfront modality to enhance graft-versus-tumor responses in high-risk patient populations.
KW - Cell therapy
KW - Leukemia
KW - Lymphoma
KW - Myeloma
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U2 - 10.1016/j.bbmt.2011.05.012
DO - 10.1016/j.bbmt.2011.05.012
M3 - Article
C2 - 21664472
AN - SCOPUS:80053210017
SN - 1083-8791
VL - 17
SP - 1679
EP - 1687
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 11
ER -