15314544

pubmed:Citation

5

MART-1(27-35)-peptide-pulsed immature dendritic cells (DCs) resulted in immunologic and clinical activity in a prior phase 1 trial. A phase 2 cohort expansion was initiated to further characterize the phenotype and cytokine milieu of the DC vaccines and their immunologic activity in vitro and to further examine a possible link between clinical activity and determinant spreading. In an open-label phase 2 trial, 10(7) autologous ex vivo generated DCs pulsed with the HLA-A*0201 immunodominant peptide MART-1(27-35) were administered to 10 subjects with stage II-IV melanoma. The experimental vaccines were administered intradermally in a biweekly schedule for a total of three injections, and blood for immunologic assays was obtained before each administration and at three time points after. DC vaccine preparations had wide intra- and interpatient variability in terms of cell surface markers and preferential cytokine milieu, but they did not correlate with the levels of antigen-specific T cells after vaccination. Of four patients with measurable disease, one had stable disease for 6 months and another has a continued complete response for over 2 years, which is confounded by receiving a closely sequenced CTLA4 blocking antibody. The DC vaccines induced determinant spreading in this subject, and CTLA4 blockade reactivated T cells with prior antigen exposure. The DC phenotype and cytokine profile do not correlate with the ability to induce antigen-specific T cells, while determinant spreading after DC immunization may be a marker of an efficient antitumor response. Sequential CTLA4 blockade may enhance the immune activity of DC-based immunotherapy.

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IM

MEDLINE

pubmed-author:AmarnaniSaral NSN, pubmed-author:ButterfieldLisa HLH, pubmed-author:Comin-AnduixBegonyaB, pubmed-author:DissetteVivian BVB, pubmed-author:EconomouJames SJS, pubmed-author:GlaspyJohn AJA, pubmed-author:LeeYohanY, pubmed-author:McBrideWilliam HWH, pubmed-author:OsegueraDeniseD, pubmed-author:RibasAntoniA, pubmed-author:SejaElisabethE, pubmed-author:TchekmedyianN SimonNS, pubmed-author:VuHuong THT, pubmed-author:WargoJennifer AJA

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NLM

354-67

pubmed-meshheading:15314544-Adult, pubmed-meshheading:15314544-Aged, pubmed-meshheading:15314544-Antibodies, Blocking, pubmed-meshheading:15314544-Antigens, CD, pubmed-meshheading:15314544-Antigens, Differentiation, pubmed-meshheading:15314544-Biological Markers, pubmed-meshheading:15314544-CTLA-4 Antigen, pubmed-meshheading:15314544-Cancer Vaccines, pubmed-meshheading:15314544-Cytokines, pubmed-meshheading:15314544-Dendritic Cells, pubmed-meshheading:15314544-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:15314544-Epitopes, pubmed-meshheading:15314544-Female, pubmed-meshheading:15314544-Humans, pubmed-meshheading:15314544-Immunotherapy, pubmed-meshheading:15314544-Isoantigens, pubmed-meshheading:15314544-Male, pubmed-meshheading:15314544-Melanoma, pubmed-meshheading:15314544-Middle Aged, pubmed-meshheading:15314544-Peptide Fragments, pubmed-meshheading:15314544-Phenotype, pubmed-meshheading:15314544-T-Lymphocytes, pubmed-meshheading:15314544-Treatment Outcome

Department of Surgery, Division of Surgical Oncology, UCLA Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California, USA.