This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noonan, K. Articles by Borrello, I. Search for Related Content PubMed PubMed Citation Articles by Noonan, K. Articles by Borrello, I.

Activated Marrow-Infiltrating Lymphocytes Effectively Target Plasma Cells and Their Clonogenic Precursors

¹ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland and ² Xcyte Therapies, Seattle, Washington

Requests for reprints: Ivan Borrello, Room 453, 1650 Orleans Street, Baltimore, MD 21231. Phone: 410-955-4967; Fax: 410-614-9705; E-mail: borreiv{at}jhmi.edu.

A major limitation of adoptive immunotherapy is the availability of T cells specific for both terminally differentiated tumor cells and their clonogenic precursors. We show here that marrow-infiltrating lymphocytes (MILs) recognize myeloma cells after activation with anti-CD3/CD28 beads with higher frequency than activated peripheral blood lymphocytes from the same patients. Furthermore, activated MILs target both the terminally differentiated CD138⁺ plasma cells and the myeloma precursor as shown by profound inhibition in a tumor clonogenic assay. The presence of antigen in the marrow microenvironment seems to be important for the maintenance of tumor specificity. Taken together, these results highlight the intrinsic tumor specificity of MILs and describe a novel approach for the generation of tumor-specific T-cell populations suitable for adoptive immunotherapy of multiple myeloma.

Key Words: Immunotherapy • multiple myeloma • marrow-infiltrating lymphocytes • lymphocyte activation • myeloma clonogenic precursors

This article has been cited by other articles:

				O. C. Goodyear, G. Pratt, A. McLarnon, M. Cook, K. Piper, and P. Moss Differential pattern of CD4+ and CD8+ T-cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma Blood, October 15, 2008; 112(8): 3362 - 3372. [Abstract] [Full Text] [PDF]

				K. M. Dhodapkar, S. Barbuto, P. Matthews, A. Kukreja, A. Mazumder, D. Vesole, S. Jagannath, and M. V. Dhodapkar Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma Blood, October 1, 2008; 112(7): 2878 - 2885. [Abstract] [Full Text] [PDF]

				C. A. Huff and W. Matsui Multiple Myeloma Cancer Stem Cells J. Clin. Oncol., June 10, 2008; 26(17): 2895 - 2900. [Abstract] [Full Text] [PDF]

				D. Atanackovic, Y. Cao, T. Luetkens, J. Panse, C. Faltz, J. Arfsten, K. Bartels, C. Wolschke, T. Eiermann, A. R. Zander, et al. CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation Haematologica, March 1, 2008; 93(3): 423 - 430. [Abstract] [Full Text] [PDF]

				Y. Dang, K. L. Knutson, V. Goodell, C. dela Rosa, L. G. Salazar, D. Higgins, J. Childs, and M. L. Disis Tumor Antigen-Specific T-Cell Expansion Is Greatly Facilitated by In vivo Priming Clin. Cancer Res., March 15, 2007; 13(6): 1883 - 1891. [Abstract] [Full Text] [PDF]

				M. Condomines, D. Hose, P. Raynaud, M. Hundemer, J. De Vos, M. Baudard, T. Moehler, V. Pantesco, M. Moos, J.-F. Schved, et al. Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis J. Immunol., March 1, 2007; 178(5): 3307 - 3315. [Abstract] [Full Text] [PDF]