The perspective of combining
cancer vaccines with
immunomodulatory drugs is currently regarded as a highly promising approach for boosting
tumor-specific T cell immunity and eradicating residual malignant cells. The efficacy of dendritic cell (DC) vaccination in combination with
lenalidomide, an anticancer
drug effective in several
hematologic malignancies, was investigated in a
follicular lymphoma (FL) model. First, we evaluated the in vitro activity of
lenalidomide in modulating the immune responses of lymphocytes co-cultured with a new DC subset differentiated with IFN-α (IFN-DC) and loaded with apoptotic
lymphoma cells. We next evaluated the efficacy of
lenalidomide and IFN-DC-based vaccination, either alone or in combination, in hu-PBL-NOD/SCID mice bearing established human
lymphoma. We found that
lenalidomide reduced Treg frequency and
IL-10 production in vitro, improved the formation of immune synapses of CD8 + lymphocytes with
lymphoma cells and enhanced anti-
lymphoma cytotoxicity. Treatment of
lymphoma-bearing mice with either IFN-DC vaccination or
lenalidomide led to a significant decrease in
tumor growth and
lymphoma cell spread.
Lenalidomide treatment was shown to substantially inhibit
tumor-induced neo-angiogenesis rather than to exert a direct cytotoxic effect on
lymphoma cells. Notably, the combined treatment with the
vaccine plus
lenalidomide was more effective than either single treatment, resulting in the significant regression of established
tumors and delayed
tumor regrowth upon treatment discontinuation. In conclusion, our data demonstrate that IFN-DC-based vaccination plus
lenalidomide exert an additive
therapeutic effect in xenochimeric mice bearing established
lymphoma. These results may pave the way to evaluate this combination in the clinical ground.