Vaccination of Metastatic Colorectal Cancer Patients With Matured Dendritic Cells Loaded With Multiple Major Histocompatibility Complex Class I Peptides

2007 ◽  
Vol 30 (7) ◽  
pp. 762-772 ◽  
Author(s):  
Brian Kavanagh ◽  
Andrew Ko ◽  
Alan Venook ◽  
Kim Margolin ◽  
Herbert Zeh ◽  
...  
1996 ◽  
Vol 184 (3) ◽  
pp. 1179-1184 ◽  
Author(s):  
Y Ke ◽  
J A Kapp

Professional antigen-presenting cells, such as macrophages, dendritic cells, or B cells, take up soluble, exogenous antigens (Ags) and process them through the class II pathway. Several reports have shown that phagocytic macrophages also process particulate or soluble forms of exogenous Ag via the class I pathway. By contrast, B cells normally do not process soluble, exogenous Ag by way of the class I pathway unless Ags are directly introduced into the cytoplasm. Here we report that B cells present exogenous Ag via the class I pathway when Ags are taken up by receptor-mediated endocytosis. Thus, specialized methods of Ag uptake such as phagocytosis or receptor-mediated endocytosis deliver exogenous Ag into the class I pathway of Ag processing and presentation.


2000 ◽  
Vol 9 (6) ◽  
pp. 1-5 ◽  
Author(s):  
Linda M. Liau ◽  
Keith L. Black ◽  
Neil A. Martin ◽  
Steven N. Sykes ◽  
Jeff M. Bronstein ◽  
...  

Dendritic cells (DCs) are antigen-presenting cells that play a central role in the initiation and modulation of antitumor immune responses. In this pilot study, we investigated the ability of autologous DCs pulsed ex vivo with allogeneic major histocompatibility complex class I–matched glioblastoma peptides to stimulate host antitumor immune responses when injected as a vaccine. A patient with recurrent brainstem glioblastoma multiforme (GBM) received a series of three intradermal immunizations of antigen-pulsed DCs on an outpatient basis following surgical debulking of her posterior fossa tumor. Dendritic cell vaccination was well tolerated, and no clinical signs of autoimmunity or experimental allergic en-cephalomyelitis were detected. She developed a measurable cellular immune response against the allogeneic glioblastoma peptides used in her vaccine preparation, as demonstrated by in vitro T-cell proliferation assays. In addition, increased T-cell infiltration was noted within the intracranial tumor site in the biopsy sample obtained following DC vaccination. An objective clinical response, however, was not evident, and this patient eventually died 21 months after her disease was diagnosed. To our knowledge, this is the first patient with brain cancer ever to be treated with DC-based immunotherapy. This case illustrates that vaccination with DCs pulsed with acid-eluted glioblastoma peptides is feasible and can induce systemic antigen-specific immunity in a patient with recurrent GBM. Additional studies are necessary to determine the optimum DC doses and antigen loading conditions that may translate into clinical effectiveness and survival benefit for patients with brain tumors. Phase I trials for malignant glioma are currently underway.


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