Informace o publikaci
Dendritic Cell Biology anf the Application of Dendritic Cells to Imunotherapy of Multiple Myeloma
| Autoři | |
|---|---|
| Rok publikování | 2000 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Medical Oncology |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Onkologie a hematologie |
| Popis | Dentritic cells (DCs)are extremely efficient antigen-presenting cells that arepotent stimulators of both B and T cell immune responses. Although DCc are normally present in extremely small numbers in the circulation, recent advances in DC biology have made it possible to generale DCs in culture. DCs can be generated in vitro from various cellular sources including bone marrow, cor blood and peripheral blood. Although culture conditions are extremely diverse, the majority of protocols grow DCs in GM-CSF and either TNF-aplha and/or IL. The addition of other growth factors such as SCF and Flt-3 ligand can dramatically enhance DC recovery. It is important to appereciate that DC subsets have been identified. Thus, DC at different stages of maturation, based on phenotype and capacity to capture antigen, can be obtained depending on culture conditions. For clinical applications, DCs can be generated in serum-free median and cryopreserved for future cclinical applications. The ability to obtain DCs in numbers suitable for manipulating immune responses has pushed DC-based immunotherapies into the spotlight for treatment of various malignancies, including multiple myeloma, a B cell malignancy that is presently incurable. Although high-dose chemotherapy and transplantation have improved cmplete remission rates and overall survival in myeloma, immunotherapeutic strategies are needed for the additional cytoreduction need to achieve a cure. Because DCs specialize in antigen capture and are extremely potent at stimulating T cell responses, they are ideally suited for generating anti-myeloma T cell responses in vivo. Several studies have demonstrated thal myeloma protein, also called idiotype (Id), is sufficiently imunogenic and can be used to generate in vivo T cell responses in myeloma patients. Clinical trials using Id-pulsed DCs as a vaccine to teeat minimal resifual disease or relapsed myeloma are currently underway. Feasibility studies indicate that antigen-pulsed autologous DCs can be used to elicit in vivo Id-specific T cell responses. Additional studies are need to optimize current DC vaccination protocols and determine clinical benefits associated with this approach. It is hope that, following conventional therapies, a combination of adoptive. |
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