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

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2872-2880
Number of pages9
JournalCancer Research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Singh, H., Serrano, L. M., Pfeiffer, T., Olivares, S., McNamara, G., Smith, D. D., Al-Kadhimi, Z., Forman, S. J., Gillies, S. D., Jensen, M. C., Colcher, D., Raubitschek, A., & Cooper, L. J. N. (2007). Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy. Cancer Research, 67(6), 2872-2880. https://doi.org/10.1158/0008-5472.CAN-06-2283