P08.01 Combined approach of adoptive cell therapy with cytokine-induced killer cells retargeted with immunotools against HER-2-expressing breast cancer

BackgroundCytokine-Induced Killer (CIK) cells are a heterogeneous effector cells CD3+ CD56+ easily to expand from PBMC and in clinically relevant numbers with phenotypic and functional properties between T and NK cells. They show MHC-unrestricted cytotoxicity against tumors and exert Antibody-depend...

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Bibliographic Details
Published in:Journal for immunotherapy of cancer 2022-09, Vol.10 (Suppl 1), p.A25-A26
Main Authors: Ventura, A, Perpinello, S, Cappuzzello, E, Dalla Pietà, A, Vigolo, E, D’Accardio, G, Peipp, M, Sommaggio, R, Rosato, A
Format: Article
Language:English
Subjects:
Bibliographic literature
Breast cancer
Cytokines
Cytotoxicity
Flow cytometry
Poster Presentations
Tumors
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Summary:BackgroundCytokine-Induced Killer (CIK) cells are a heterogeneous effector cells CD3+ CD56+ easily to expand from PBMC and in clinically relevant numbers with phenotypic and functional properties between T and NK cells. They show MHC-unrestricted cytotoxicity against tumors and exert Antibody-dependent Cellular Cytotoxicity (ADCC) when combined with monoclonal antibodies (mAbs).1,2 In the present study, we evaluated the enhancement of CIK cell killing capacity due to the combination with either the clinical used mAb Trastuzumab (TRS) and its optimized form TRS V90Lec13, or with the bispecific antibody (bsAb) HER2xCD3, against HER-2+ breast cancer cells.Materials and MethodsCIK cells were expanded from PBMCs of healthy donors by the addition of IFN-γ, OKT-3 and IL-2. The immunotools binding proprieties on target and CIK cells were determined by flow cytometry. The CIK cell cytotoxicity and the dose-dependent activity of HER2xCD3 and TRS V90lec13 were evaluated with a 4-hours Calcein-AM assay or with a 40/60-hours real-time cell assay against HER-2+ breast cancer cell lines. The concentration of cytokines produced upon the 20-hours co-colture of effector with target cells was assessed with a multiplex assay by flow cytometry analysis. The in vivo biodistribution of the fluorophore- conjugated HER2xCD3 bsAb was monitored in tumor bearing NSG mouse model.ResultsHER2xCD3 binds efficiently to CIK cells with the ScFv of CD3 and to cancer cells with the ScFv of HER-2 in a dose-dependent manner. The specific combination of HER2xCD3, TRS or TRS V90lec13 with CIK cells significant enhances their anti-tumor activity against several breast cancer cell lines, compared to CIK cells alone, even at a very low effector/target ratio (0.1:1). Interestingly, TRS-resistant tumor cell lines show to be sensitive instead to HER2xCD3-redirected CIK cell lytic activity. The increase of CIK cell killing is correlated to the dose of bsAb and it is functional even at very low concentrations. Moreover, redirected-CIK cells presents a proinflammatory and not a toxic cytokines profile. The bsAb HER2xCD3 arrives efficiently at the tumor site where reaches the maximum concentration after 8 hours of injection into mice.ConclusionsThese results highlight the potentiality of using clinical grade mAbs or recombinant immunotools to improve the cytotoxic activity of CIK cells against HER-2+ tumor cells, opening new perspectives for adoptive immunotherapy to treat solid tumors.ReferencesADDIN Mend
ISSN:2051-1426
DOI:10.1136/jitc-2022-ITOC9.47