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CD40-activated B cells can be generated in high number and purity in cancer patients: analysis of immunogenicity and homing potential
- Source :
- Clinical and experimental immunology. 155(2)
- Publication Year :
- 2008
-
Abstract
- SummaryCellular 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.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Immunology
Antigen presentation
C-C chemokine receptor type 7
Basic Studies
Biology
Major histocompatibility complex
Lymphocyte Activation
Cancer Vaccines
Immunophenotyping
Antigen
Neoplasms
Immunology and Allergy
Humans
CD40 Antigens
Antigen-presenting cell
Carcinoma, Renal Cell
Antigen Presentation
B-Lymphocytes
CD40
Prostatic Neoplasms
Dendritic Cells
Kidney Neoplasms
Chemotaxis, Leukocyte
Colonic Neoplasms
biology.protein
Lymphocyte Culture Test, Mixed
Homing (hematopoietic)
Subjects
Details
- ISSN :
- 13652249
- Volume :
- 155
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Clinical and experimental immunology
- Accession number :
- edsair.doi.dedup.....1b06d5d6689dd9bb81141dceae0b95f1