Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on 10 patients with resected American Joint Committee on Cancer (AJCC)stage IIA-IIIC melanoma receiving individualized adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, gp100 and tyrosinase, according to patient tumor associated HLA restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Except for 1 patient, all patients had received systemic pretreatment with immunotherapy (n = 8), chemoimmunotherapy (n = 1), chemotherapy (n = 1), or cefalectin therapy (n = 1). Upon prior therapy, 7 of 10 patients had progressed with subcutaneous/cutaneous (n = 2), lymph node (n = 3), or subcutaneous/cutaneous and lymph node (n = 2)metastases, which were subsequently resected prior to vaccination. After a mean of 6.5 vaccination cycles, progression-free survival was 6 months (median, range 2-10). Five patients were relapse-free for 1+ up to 21+ months, 3 patients developed a solitary cutaneous metastasis, and 2 patients developed multiple metastases during vaccination. Overall, vaccine treatment was well tolerated, with no severe side-effects. Eight of 10 patients developed local delayed type hypersensitivity (DTH)reactions to synthetic peptides after the first or second injection. In 2 patients, transient fever, nausea, diarrhea, and muscle pain of National Cancer Institute (NCI)Grade I occurred. In summary, individualized synthetic peptide vaccination, combined with GM-CSF, was feasible and warrants further clinical investigation.
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PMID:Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients. 1566 24

Approaches facilitating generation of dendritic cell (DC) vaccines for clinical trials and enhancing their viability, bio-distribution, and capacity to stimulate antigen-specific immune responses are critical for immunotherapy. We programmed mouse bone marrow (BM) cells with lentiviral vectors (LV-GI4) so that they produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in an autonomous manner. DC/LV-GI4 cells underwent autonomous trans-differentiation to yield typical phenotypic characteristics of DCs. DC/LV-GI4 cells that self-differentiated either ex vivo or in vivo showed persistent and robust viability and stimulated high influx of DCs into draining lymph nodes (LNs). The immunostimulatory efficacy of DC/LV-GI4 cells was evaluated using MART1 and TRP2 as co-expressed melanoma antigens. Mice vaccinated with DC/LV-GI4 cells that self-differentiated in vitro or in vivo produced potent antigen-specific responses against melanoma, which correlated with protective and long-term therapeutic anti-tumor effects. Thus, DC precursors can be genetically engineered after a single ex vivo manipulation, resulting in DC vaccines with improved activity.
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PMID:Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines. 1744 71

Twenty-four (24) pretreated patients with relapsed high-risk resected The American Joint Committee on Cancer (AJCC) stage IIA-IV melanoma received adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, MAGE-1, gp100, and tyrosinase, according to patient tumor-associated human leukocyte antigen (HLA) restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Pretreatment was comprised of surgery (n=23 primary tumor; n=23 metastases), local radiotherapy (n=2), immunotherapy (n=23), chemotherapy (n=10), and chemoimmunotherapy (n=1), respectively. All patients received peptide vaccines in an adjuvant setting. Seven (7) patients were relapse free for 3+ up to 25+ months. Of the patients exhibiting progressive disease (n=17), 13 patients developed metastases during vaccination (9 local, 4 distant), and 4 patients developed metastases (2 local, 2 distant) after finishing vaccine therapy. Two (2)-year local and distant metastases-free survival, 2-year distant metastases-free survival, and 2-year overall survival were calculated as 8.6%, 68%, and 85%, respectively. Vaccine treatment was well tolerated, with no severe side-effects. Twenty (20) of 24 patients developed local delayed-type hypersensitivity (DTH) reactions to synthetic peptide vaccination. Transient fever (n=2) and pain in muscle/bone (n=2) occurred rarely. In conclusion, antigenic peptide vaccination, combined with GM-CSF, is safe and may yield clinical benefits in relapsed high-risk resected melanoma patients.
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PMID:GM-CSF plus antigenic peptide vaccination in locally advanced melanoma patients. 1780 50