Back to Search
Start Over
Cord blood-derived cytokine-induced killer cells combined with blinatumomab as a therapeutic strategy for CD19
- Source :
- Cytotherapy. 20(8)
- Publication Year :
- 2017
-
Abstract
- Background Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19+ malignancies. Methods CB-CIKs were expanded in vitro and fully characterized in comparison with peripheral blood (PB)–derived CIKs. Results CB-CIKs, like PB-CIKs, were mostly CD3+ T cells with mean 45% CD3+CD56+ and expressing mostly TCR(T cell receptor)αβ with a TH1 phenotype. CB-CIK cultures had, however, a larger proportion of CD4+ cells, mostly CD56−, as well as a greater proportion of naive CCR7+CD45RA+ and a lower percentage of effector memory cells, compared with PB-CIKs. CB-CIKs were very similar to PB-CIKs in their expression of a large panel of co-stimulatory and inhibitory/exhaustion markers, except for higher CD28 expression among CD8+ cells. Like PB-CIKs, CB-CIKs were highly cytotoxic in vitro against natural killer (NK) cell targets and efficiently lysed CD19+ tumor cells in the presence of blinatumomab, with 30–60% lysis of target cells at very low effector:target ratios. Finally, both CB-CIKs and PB-CIKs, combined with blinatumomab, showed significant therapeutic activity in an aggressive PDX Ph+ CD19+ acute lymphoblastic leukemia model in NOD-SCID mice, without sign of toxicity or graft-versus-host disease. The improved expansion protocol was finally validated in good manufacturing practice conditions, showing reproducible expansion of CIKs from cryopreserved cord blood units with a median of 28.8 × 106 CIK/kg. Discussion We conclude that CB-CIKs, combined with bispecific T-cell–engaging antibodies, offer a novel, effective treatment strategy for leukemia.
- Subjects :
- 0301 basic medicine
Cytotoxicity, Immunologic
Male
Cancer Research
Immunology
Antigens, CD19
Mice, Transgenic
Mice, SCID
CD8-Positive T-Lymphocytes
Immunotherapy, Adoptive
CD19
03 medical and health sciences
Mice
0302 clinical medicine
Antineoplastic Agents, Immunological
Cytokine-Induced Killer Cells
Mice, Inbred NOD
Neoplasms
Antibodies, Bispecific
medicine
Immunology and Allergy
Cytotoxic T cell
Animals
Humans
Genetics (clinical)
Transplantation
Cytokine-induced killer cell
biology
Chemistry
Infant, Newborn
CD28
Cell Biology
medicine.disease
Fetal Blood
Combined Modality Therapy
Killer Cells, Natural
Leukemia
030104 developmental biology
Treatment Outcome
Oncology
Cord blood
Cancer research
biology.protein
Blinatumomab
Female
K562 Cells
CD8
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 14772566
- Volume :
- 20
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cytotherapy
- Accession number :
- edsair.doi.dedup.....8fd4dc964f522ebc407eb66c7466ef49