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 S 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 Citations (Scopus)

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

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Interleukin-2
T-Lymphocytes
Neoplasms
Biological Therapy
Tumor Microenvironment
Adoptive Transfer
Hematopoietic Stem Cell Transplantation
Cell- and Tissue-Based Therapy
Fetal Blood
Immunotherapy
B-Lymphocytes
Therapeutics
Monoclonal Antibodies
Clinical Trials
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Singh, H., Serrano, L. M., Pfeiffer, T., Olivares, S., McNamara, G., Smith, D. D., ... 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

Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy. / Singh, Harjeet; Serrano, Lisa Marie; Pfeiffer, Timothy; Olivares, Simon; McNamara, George; Smith, David D.; Al-Kadhimi, Zaid S; Forman, Stephen J.; Gillies, Stephen D.; Jensen, Michael C.; Colcher, David; Raubitschek, Andrew; Cooper, Laurence J.N.

In: Cancer Research, Vol. 67, No. 6, 15.03.2007, p. 2872-2880.

Research output: Contribution to journalArticle

Singh, H, Serrano, LM, Pfeiffer, T, Olivares, S, McNamara, G, Smith, DD, Al-Kadhimi, ZS, Forman, SJ, Gillies, SD, Jensen, MC, Colcher, D, Raubitschek, A & Cooper, LJN 2007, 'Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy', Cancer Research, vol. 67, no. 6, pp. 2872-2880. https://doi.org/10.1158/0008-5472.CAN-06-2283
Singh, Harjeet ; Serrano, Lisa Marie ; Pfeiffer, Timothy ; Olivares, Simon ; McNamara, George ; Smith, David D. ; Al-Kadhimi, Zaid S ; Forman, Stephen J. ; Gillies, Stephen D. ; Jensen, Michael C. ; Colcher, David ; Raubitschek, Andrew ; Cooper, Laurence J.N. / Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy. In: Cancer Research. 2007 ; Vol. 67, No. 6. pp. 2872-2880.
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