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Case Reports
. 2024 Sep 1;109(9):3037-3041.
doi: 10.3324/haematol.2023.284881.

A rescue approach in refractory diffuse large B-cell lymphoma with obinutuzumab-redirected cytokineinduced killer cells: a first-in-human case report

Francesca Elice  1 , Roberta Sommaggio  2 , Elisa Cappuzzello  3 , Marcello Riva  1 , Maria Chiara Tisi  1 , Martina Bernardi  4 , Angela Bozza  4 , Daniela Catanzaro  4 , Katia Chieregato  4 , Anna Merlo  4 , Ilaria Giaretta  1 , Anna Dalla Pieta  5 , Mauro Krampera  6 , Carlo Visco  6 , Livio Trentin  7 , Andrea Visentin  7 , Alberto Tosetto  1 , Giuseppe Astori  4 , Antonio Rosato  2
Affiliations
Case Reports

A rescue approach in refractory diffuse large B-cell lymphoma with obinutuzumab-redirected cytokineinduced killer cells: a first-in-human case report

Francesca Elice et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Monoclonal antibody-mediated cytokine-induced killer cell retargeting. The combination of cytokine-induced killer cells with clinical-grade anti-CD20 monoclonal antibodies, such as obinutuzumab, polarizes their activity in an antigen-specific manner and prompts antibody-dependent cell-mediated cytotoxicity. Figure created with BioRender.com. CIK: cytokine-induced killer; NKG2D: natural killer group 2 D; ADCC: antibody-dependent cell-mediated cytotoxicity.
Figure 2.
Figure 2.
CIK_D332 production and infusion protocol. (A) CIK_D332 were generated using a blinatumomab-based cell culture protocol in the presence of interferon-γ, CD3 (OKT3) monoclonal antibody, and interleukin-2 for 14 days in G-Rex flasks (Wilson Wolf, Saint Paul, MN, USA). The infusion product was evaluated prior to cryopreservation by (B) multi-color flow cytometry to characterize the phenotype and by (C) a calcein-AM release assay against the K562 cell line to determine the cytotoxic activity at different effector-to-target cell ratios. (D) The patient was infused at 14-day intervals with escalating doses of CIK_D332 from 1x106 to 3x106 cells/kg. The day before each infusion, the patient was given the anti-CD20 monoclonal antibody obinutuzumab (1,000 mg). Figure created with BioRender.com. PBMC: peripheral blood mononuclear cells; IFN-γ: interferon-gamma; IL-2: interleukin-2; mAB: monoclonal antibody; QC: quality control; SSC: side scatter; 7-AAD: 7-amino actinomycin D; E:T: effector-to-target cell ratio; CIK: cytokine-induced killer.
Figure 3.
Figure 3.
Clinical markers after CIK_D332 infusion. (A-C) Post-infusion trends of serum C-reactive protein (A), plasma cytokines (B), and white blood cells, neutrophils and platelets (C). Arrows indicate the times of administration of the combined cytokine-induced killer cell and obinutuzumab treatments, as detailed in Figure 2D. (D, E) Positron emission tomography scans were performed before (D) and 1 month after (E) the treatment. Arrows indicate the involved lymph nodes. CRP: C-reactive protein; IFN-γ: interferon-gamma; IL: interleukin; TNF-α: tumor necrosis factor-alpha; IFN-α: interferon-alpha; GM-CSF: granulocyte-monocyte – colony-stimulating factor; WBC: white blood cells.
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References

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