The development of a bi-specific Anti-CD161A x anti-tumor antibody for rat NK cell targeting

Martin Hagenaars, N. Geeske Ensink, Liesbeth E. Jonges, William H. Chambers, Alexander M.M. Eggermont, Cornelis J.H. Van De Velde, Gert Jan Fleuren, Peter J.K. Kuppen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

7 Citaten (Scopus)


In order to improve the therapeutic efficacy of adoptive immunotherapy of cancer using IL-2-activated NK (A-NK) cells, we developed a bi-specific monoclonal antibody (BimAb) 3.2.3 x CC52. One specificity of the BimAb (mAb 3.2.3) was directed against rat CD161A (NKR-P1A) which has been shown to be an activation structure on rat NK cells involved in lysis of target cells and cytokine secretion. The other specificity (mAb CC52) was directed against a tumor associated antigen on the rat colon adenocarcinoma cell line CC531. The hybridomas producing 3.2.3 and CC52 were fused, resulting in a quadroma producing the desired 3.2.3 x CC52 BimAb. The hybridomas produced antibodies of different isotypes (IgG2b and IgG1 respectively) which enabled us to pre-select quadromas with a high likelihood for production of BimAb, through testing for the production of bi-isotypic antibodies. Production of functional BimAb by the selected quadromas was demonstrated in an assay showing enhanced conjugate formation between CD161A+ cells and CC531 tumor cells. We also tested the 3.2.3 x CC52 BimAb for its capacity to enhance NK cell-mediated lysis of CC531 tumor cells in 4 h and 19 h 51Cr release assays; in a prolonged (2 day) tumor neutralization assay using a terrazolium salt (MTT)-based assay; and in tests for apoptosis using Annexin V-FITC. Although this BimAb was not demonstrated to cause enhanced lysis of CC531 cells by CD161A+ effector cells in vitro, it might be a useful tool to enhance the number of NK cells at the tumor site and/or prolong contact between tumor cells and NK cells in vivo, thereby probably enhancing the therapeutic efficacy of NK cells.

Originele taal-2Engels
Pagina's (van-tot)31-48
Aantal pagina's18
Nummer van het tijdschrift1
StatusGepubliceerd - feb. 1999
Extern gepubliceerdJa


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