IngentaConnect Immunomodulatory drugs stimulate natural killer-cell function, al...

Authors: Reddy, Nishitha; Hernandez-Ilizaliturri, Francisco J.; Deeb, George¹; Roth, Mark¹; Vaughn, Mary²; Knight, Joy¹; Wallace, Paul³; Czuczman, Myron S.

Source: British Journal of Haematology, Volume 140, Number 1, January 2008 , pp. 36-45(10)

Publisher: Blackwell Publishing

Abstract:

Summary

The immunomodulatory drugs (IMiDs) lenalidomide and actimid (also known as CC-4047) are thalidomide analogues which are more potent than their parental compound. In combination with rituximab, we have previously demonstrated that IMiDs have synergistic in vivo anti-tumour activity in preclinical studies in a human lymphoma severe combined immunodeficiency mouse model. This report further explored the mechanisms by which IMiDs exert their anti-lymphoma effects. Following exposure of subcutaneous lymphoma tumours in murine models to IMiDs, there was a significant increase in the recruitment of natural killer (NK) cells to tumour sites. This increase in NK cells was mediated via stimulation of dendritic cells and modification of the cytokine microenvironment associated with an increase in monocyte chemotactic protein-1, tumour necrosis factor-α and interferon-γ and probably augmented rituximab-associated antibody-dependent cellular cytotoxicity. IMiDs also had significant anti-angiogenic effects in our B-cell lymphoma models. Thus, by modulation of the immune system mediated via dendritic cells and NK cells, changing the cytokine milieu, as well as by their anti-angiogenic effects, IMiDs in combination with rituximab resulted in augmented in vivo anti-tumour effects against B-cell lymphoma. Our positive preclinical data adds additional support for the evaluation of IMiDs plus rituximab in patients with relapsed/refractory B-cell lymphoma.

Keywords: immunomodulatory drugs; rituximab; natural killer cells; anti-angiogenesis; dendritic cells

Document Type: Research article

DOI: 10.1111/j.1365-2141.2007.06841.x

Affiliations: 1: Immunology 2: Pathology 3: Flow Cytometry, Roswell Park Cancer Institute, Buffalo, NY, USA

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$50.16 plus tax Refund Policy

Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo