The apoptotic and proliferative fate of cytokine-induced killer cells after redirection to tumor cells with bispecific Ab

Cytotherapy
Martin KornackerRs Negrin

Abstract

Cytokine-induced killer (CIK) cells are ex vivo expanded T cells with co-expression of CD3 and CD56 and NK activity. They have recently been evaluated in a phase I/II clinical trial against malignant lymphoma. Bispecific Ab (bsAb) redirect CIK cells to tumor targets, thus enhancing their cytotoxicity. While bsAb may improve T-cell mediated anti-tumor activity, little is known about the fate of effector cells upon redirection to tumor targets using a bsAb. Using ex vivo-activated CIK cells, Her2/neu expressing breast and ovarian cell lines and a F(ab')2 Her2/neu x CD3 bsAb, we investigated the anti-tumor activity and the proliferative and apoptotic outcome of CIK cells. When redirected to tumor targets with bsAb, there was a significant increase in anti-tumor activity as well as an increase in both CIK cell proliferation and apoptosis. The addition of agonistic Ab against CD28 did not significantly increase proliferation or apoptosis of CIK cells redirected to CD80- and CD86- tumor targets. To attempt to reduce T-cell apoptosis, we incubated CIK cells in the presence of the pan-caspase inhibitor z-VAD-fmk, which led to a partial reduction in T-cell apoptosis without increasing cellular cytotoxicity. bsAb are effective in redirec...Continue Reading

References

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Citations

May 22, 2013·Journal of Cancer Research and Clinical Oncology·Qiuling LiuPatricia Elena Kunda
Apr 17, 2012·Expert Opinion on Biological Therapy·Giulia MesianoDario Sangiolo
Apr 22, 2006·Cytotherapy·A J Barrett, J Wolchok
Nov 13, 2007·International Immunopharmacology·Hwan Mook KimSang-Bae Han
Dec 7, 2006·Neuroimaging Clinics of North America·Christopher H Contag

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