CD40-activated B cells can be generated in high number and purity in cancer patients

Analysis of immunogenicity and homing potential

E. Kondo, L. Gryschok, N. Klein-Gonzalez, S. Rademacher, M. R. Weihrauch, T. Liebig, A. Shimabukuro-Vornhagen, M. Kochanek, A. Draube, M. S. Von Bergwelt-Baildon

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Cellular adjuvants such as dendritic cells (DC) are in the focus of tumour immunotherapy. In DC-vaccine trials, induction of tumour antigen-specific immunity is observed frequently and well-documented clinical responses have been reported. However, the overall response rate is less than 3%, therefore alternative strategies are being investigated. CD40-activated B cells (CD40-B) have been characterized previously as an interesting alternative because they present antigen efficiently and can be expanded by several logs from small amounts of peripheral blood. To determine the central technical challenges of cell-based vaccines we performed a single-patient analysis of 502 patients from DC-based tumour vaccine trials and identified at least three factors contributing to their limited efficiency: (1) lack of cell numbers; (2) lack of documented purity thus high contamination of bystander cells; and (3) lack of quality control and thus heterogeneous or unknown expression of important surface molecules such as major histocompatibility complex (MHC) and chemokine receptors. Based on these findings we re-evaluated the CD40-B approach in cancer patients. Here, we show that proliferation of B cells from cancer patients is equivalent to that observed in healthy donors. Purity is always > 90% after 2 weeks and remains stable for several weeks. They have comparable antigen-presenting capability determined phenotypically and by allogeneic mixed lymphocyte reaction. Expression of CCR7 and CD62L was detected in all samples and B cells migrated towards the relevant homing chemokines. Taken together, CD40-B cells from cancer patients can be expanded in virtually unlimited numbers at high purity and full function concerning antigen-presentation and migratory properties.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalClinical and Experimental Immunology
Volume155
Issue number2
DOIs
Publication statusPublished - Feb 2009
Externally publishedYes

Fingerprint

B-Lymphocytes
Dendritic Cells
Neoplasms
Vaccines
Antigens
Mixed Lymphocyte Culture Test
Cancer Vaccines
Chemokine Receptors
Antigen Presentation
Neoplasm Antigens
Major Histocompatibility Complex
Chemokines
Quality Control
Immunotherapy
Immunity
Cell Count
Tissue Donors

Keywords

  • Antigen-presenting cells
  • CD40-activated B cells
  • Tumour immunothrapy

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Kondo, E., Gryschok, L., Klein-Gonzalez, N., Rademacher, S., Weihrauch, M. R., Liebig, T., ... Von Bergwelt-Baildon, M. S. (2009). CD40-activated B cells can be generated in high number and purity in cancer patients: Analysis of immunogenicity and homing potential. Clinical and Experimental Immunology, 155(2), 249-256. https://doi.org/10.1111/j.1365-2249.2008.03820.x

CD40-activated B cells can be generated in high number and purity in cancer patients : Analysis of immunogenicity and homing potential. / Kondo, E.; Gryschok, L.; Klein-Gonzalez, N.; Rademacher, S.; Weihrauch, M. R.; Liebig, T.; Shimabukuro-Vornhagen, A.; Kochanek, M.; Draube, A.; Von Bergwelt-Baildon, M. S.

In: Clinical and Experimental Immunology, Vol. 155, No. 2, 02.2009, p. 249-256.

Research output: Contribution to journalArticle

Kondo, E, Gryschok, L, Klein-Gonzalez, N, Rademacher, S, Weihrauch, MR, Liebig, T, Shimabukuro-Vornhagen, A, Kochanek, M, Draube, A & Von Bergwelt-Baildon, MS 2009, 'CD40-activated B cells can be generated in high number and purity in cancer patients: Analysis of immunogenicity and homing potential', Clinical and Experimental Immunology, vol. 155, no. 2, pp. 249-256. https://doi.org/10.1111/j.1365-2249.2008.03820.x
Kondo, E. ; Gryschok, L. ; Klein-Gonzalez, N. ; Rademacher, S. ; Weihrauch, M. R. ; Liebig, T. ; Shimabukuro-Vornhagen, A. ; Kochanek, M. ; Draube, A. ; Von Bergwelt-Baildon, M. S. / CD40-activated B cells can be generated in high number and purity in cancer patients : Analysis of immunogenicity and homing potential. In: Clinical and Experimental Immunology. 2009 ; Vol. 155, No. 2. pp. 249-256.
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