title: Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy.
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.
authors.affiliation: Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, USA.
authors.forename: Harjeet
authors.initials: H
authors.lastname: Singh
authors.forename: Lisa Marie
authors.initials: LM
authors.lastname: Serrano
authors.forename: Timothy
authors.initials: T
authors.lastname: Pfeiffer
authors.forename: Simon
authors.initials: S
authors.lastname: Olivares
authors.forename: George
authors.initials: G
authors.lastname: McNamara
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.forename: Zaid
authors.initials: Z
authors.lastname: Al-Kadhimi
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gillies
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.forename: Andrew
authors.initials: A
authors.lastname: Raubitschek
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D020014:K562 Cells; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D018796:Immunoconjugates; D007376:Interleukin-2