Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy

Harjeet Singh, Lisa Marie Serrano, Timothy Pfeiffer, Simon Olivares, George McNamara, David D Smith, Zaid Al-Kadhimi, Stephen J Forman, Stephen D Gillies, Michael C Jensen, David Colcher, Andrew Raubitschek, Laurence J N Cooper
Cancer Research 2007 March 15, 67 (6): 2872-80
Currently, the lineage-specific cell-surface molecules CD19 and CD20 present on many B-cell malignancies are targets for both antibody- and cell-based therapies. Coupling these two treatment modalities is predicted to improve the antitumor effect, particularly for tumors resistant to single-agent biotherapies. This can be shown using an immunocytokine, composed of a CD20-specific monoclonal antibody fused to biologically active interleukin 2 (IL-2), combined with ex vivo expanded human umbilical cord blood-derived CD8(+) T cells, that have been genetically modified to be CD19 specific, for adoptive transfer after allogeneic hematopoietic stem-cell transplantation. We show that a benefit of targeted delivery of recombinant IL-2 by the immunocytokine to the CD19(+)CD20(+) tumor microenvironment is improved in vivo persistence of the CD19-specific T cells, and this results in an augmented cell-mediated antitumor effect. Phase I trials are under way using anti-CD20-IL-2 immunocytokine and CD19-specific T cells as monotherapies, and our results warrant clinical trials using combination of these two immunotherapies.

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