Biomedical subjects

Hong-Ming Hu

Publications and source records attributed to Hong-Ming Hu.

21 records · Page 2Linked to original sources

PubMedDate not supplied

Identification of tumor-specific antibodies in patients with breast cancer vaccinated with gene-modified allogeneic tumor cells.

Thirty HLA-A2 women with metastatic breast cancer received up to 14 vaccinations with MDA-MB-231-CD80, an HLA-A2 allogeneic breast cancer cell line, which had been lipofected with the cDNA for the CD80 costimulatory molecule. Tumor cells were administered with BCG or GM-CSF as an adjuvant. Sera obtained before and after vaccination were analyzed for antibodies to tumor cell lysate, MUC1, HER2/neu and p53. Since the cell line was grown in fetal bovine serum (FBS), sera were also analyzed for antibodies to FBS. Eighteen of 24 patients for whom sera were available exhibited anti-FBS activity at baseline. Eleven of these 18 patients and all six patients without baseline anti-FBS activity showed an increased titer after vaccination. The anti-FBS activity required that serum samples be absorbed in excess FBS to detect specific antibodies to tumor cell lysate. A two-fold increase in the titer of IgG specific to tumor cell lysate was observed in 6 patients. Eight of 24 patients made an antibody response to HER-2/neu, four of 24 to MUC1 and one of 24 to p53. Although antibody production to a variety of tumor cell-associated antigens was detected our results suggest that a whole cell vaccine comprising a CD80-transfected allogeneic breast cancer cell line with adjuvant BCG or GM-CSF was not a reliable method to induce significant antibody responses in women with advanced breast cancer.

Aged↗

PubMedDate not supplied

Immunological monitoring of patients with melanoma after peptide vaccination using soluble peptide/HLA-A2 dimer complexes.

To facilitate the immunologic monitoring of a peptide vaccine trial, a novel, empty dimeric HLA-A2 molecule (A2 dimer) that could be loaded with peptides was produced. The dimer comprises the extracellular domain of HLA-A2 noncovalently linked to a fusion protein consisting of human beta2-microglobulin joined to the human IgG1 Fc domain. Peptide-loaded dimer complexes were used to assess the function of peptide-specific T cells. HLA-A2 gp100 peptide dimers stimulated interferon (IFN)-gamma production by the gp100-specific TIL-1520 cell line. Gp100/A2 dimer stimulation in combination with intracellular cytokine staining was used to analyze peptide-specific T-cell responses in patients with melanoma after vaccination with the modified gp100: 209-2M peptide in adjuvant. Titration analysis of the amount of peptide-loaded dimer required to stimulate gp100-specific T cells was used to estimate the functional avidity of effector/memory CD8+ T lymphocytes. The number of peptide-specific T cells detected in the peripheral blood of vaccinated patients using this assay was comparable to the number determined by staining with fluoresceinated gp100: 209-2M HLA-A2 tetramers. IFN-gamma production by T cells was comparable after stimulation with peptide-pulsed dimers, T2 cells, or autologous dendritic cells. Peptide-loaded A2 dimers could also be used directly to stimulate T cells in the ELISPOT assay.

Animals↗

PubMedDate not supplied

Efficacy of GM-CSF-producing tumor vaccine after docetaxel chemotherapy in mice bearing established Lewis lung carcinoma.

In this report, we evaluated the efficacy of a GM-CSF-producing tumor vaccine given before and after docetaxel in mice bearing established lung tumors. Mice bearing established 3LL tumors were treated with docetaxel and tumor vaccines transduced with either control or GM-CSF adenoviral vectors. Docetaxel (5-20 mg/kg) treatment alone had only a minimal effect on growth of established 3LL tumors in vivo, although docetaxel was cytotoxic to 3LL cells in vitro. When mice bearing established 3LL tumors were pretreated with docetaxel followed by vaccination with irradiated GM-CSF- transduced 3LL tumor cells, significant tumor regression and prolonged survival were observed compared with chemotherapy alone. Delaying docetaxel treatment until after tumor vaccination abrogated the vaccine's anti-tumor effects. Mice that survived treatment were able to resist a lethal rechallenge of 3LL tumor cells. Memory CTL specific for an epitope (MUT-1) derived from 3LL were detected in surviving mice. Docetaxel induced a mild lymphodepletion in mice, both CD4 and CD8 subsets were reduced in LN and spleens. Interestingly, docetaxel also diminished the number of memory CD8+ T cells (CD122+) and possible CD4+ CD25+ Foxp3+ natural Treg cells. Docetaxel treatment did not affect antigen-driven proliferation of naive T cells but significantly promoted survival of activated T cells. Thus, augmentation of vaccine induced antitumor immunity in docetaxel-treated mice primarily due to the enhanced survival of antigen-experienced T cells.

Adenoviridae↗