Table 2 Preclinical studies with the combination of lenalidomide and rituximab in NHL

Hernandez-Ilizaliturri et al. [22]

Raji (Burkitt lymphoma) and SU-DHL-4 and SU-DHL-10 (DLBCL) cells

SCID mouse (Burkitt Lymphoma)

• Len augmented NK cell function and increased anti-tumor effects of Rtx against B-cell lymphomas.

• Len-Rtx enhanced anti-tumor activity in SCID-mouse lymphoma model.

Wu et al. [13]

Raji and Namalwa (Burkitt lymphoma), Farage (DLBCL), Jeko-1 (MCL), and primary B-CLL cells

-

• Len enhanced NK cell- and monocyte-mediated ADCC of Rtx-treated CD20+ tumor cells.

• Len has strong potential to enhance Rtx-mediated killing of NHL cell lines.

Reddy et al. [23]

Raji (Burkitt lymphoma) cells

SCID mouse (Burkitt Lymphoma)

• Len-Rtx enhanced anti-tumor effects.

• These effects were caused by modulation of the immune system mediated by dendritic cells and NK cells, which changed the cytokine milieu, and by their anti-angiogenic effects.

Gaidarova et al. [54]

Jeko-1 (MCL) cells

-

• Len-Rtx treatment of MCL cells enhanced NK cell-mediated synapse formation and cell killing.

Gandhi et al. [55]

DoHH-2 (FL), Rec-1 (MCL), Farage (DLBCL), and fresh FL cells

• Len-Rtx induced anti-proliferative and anti-apoptotic effects in FL cells in vitro and in vivo through Bcl-2 activation.

Zhang et al. [21]

SP53, MINO, Grant 519 cells (MCL) and fresh patient samples (MCL)

SCID mouse (MCL)

• Len-Rtx had a synergistic therapeutic effect on MCL cells by enhancing apoptosis and Rtx-dependent NK cell-mediated cytotoxicity.

• Len-Rtx decreased tumor burden and prolonged survival of MCL-bearing SCID mice.

Gaidarova et al. [56]

Jeko-1 (MCL) and B-CLL cells

-

• Len induced capping of CD20 and cytoskeletal proteins to enhance Rtx immune recognition of malignant B-cells.