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Biomedical subjects

E S Schultz

Publications and source records attributed to E S Schultz.

10 recordsLinked to original sources

Dendritic cell-based immunotherapy.

Dendritic cell (DC)-based vaccinations represent a promising approach for the immunotherapy of cancer and infectious diseases as DCs play an essential role in initiating cellular immune responses. A number of clinical trials using ex vivo-generated DCs have been performed so far and only minor toxicity has been reported. Both the induction of antigen-specific T cells and clinical responses have been observed in vaccinated cancer patients. Nevertheless, DC-based immunotherapy is still in its infancy and there are many issues to be addressed such as antigen loading procedures, DC source and maturational state, migration properties, route, frequency, and dosage of DC vaccination. The increasing knowledge of DC biology should be used to improve the efficacy of this new therapy.

Animals↗

A MAGE-3 peptide presented by HLA-B44 is also recognized by cytolytic T lymphocytes on HLA-B18.

Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because of their tumoral specificity and because they are shared by many tumors. Antigenic peptide MEVDPIGHLY, which is encoded by MAGE-3 and is known to be presented by human leukocyte antigen (HLA)-B44, is currently being used in therapeutic vaccination trials. We report here that a cytolytic T lymphocyte (CTL) clone, which is restricted by HLA-B*1801, recognizes the same peptide and, importantly, lyzes HLA-B18 tumor cells expressing MAGE-3. These results imply that the use of peptide MEVDPIGHLY can now be extended to HLA-B18 patients. We also provide evidence that, under limiting amounts of protein MAGE-3, HLA B*1801 and B*4403 compete for binding to the peptide.

Antigen Presentation↗

A MAGE-1 peptide recognized on HLA-DR15 by CD4(+) T cells.

Antigens encoded by MAGE genes and recognized by T cells are of interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. Several MAGE-1 peptide that are recognized by CD8(+) cytolytic T lymphocytes have been used in therapeutic vaccination trials. To obtain anti-tumor immune response, vaccines combining peptides recognized by CD8(+) and peptides recognized by CD4(+) T cells might be optimal. We focused therefore on the identification of MAGE peptides recognized by CD4(+) T cells. We report here the identification of MAGE-1 epitope EYVIKVSARVRF, which is presented to CD4(+) T lymphocytes by HLA-DR15. This HLA allele is present in 29 % of Asians and 17 % of Caucasians.

Antigen Presentation↗

A MAGE-3 peptide recognized on HLA-B35 and HLA-A1 by cytolytic T lymphocytes.

Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. Antigenic peptide EVDPIGHLY encoded by MAGE-3 and known to be presented by HLA-A*0101 is currently being used in therapeutic vaccination trials. We report here that a cytolytic T-lymphocyte (CTL) clone, which is restricted by HLA-B*3501, recognizes the same peptide and, importantly, lyses HLA-B*3501 tumor cells expressing MAGE-3. These results infer that the current clinical use of peptide EVDPIGHLY can now be extended to HLA-B*3501 patients.

Amino Acid Sequence↗

A MAGE-A3 peptide presented by HLA-DP4 is recognized on tumor cells by CD4+ cytolytic T lymphocytes.

Antigens encoded by MAGE-A3 and recognized by T cells are interesting targets for tumor immunotherapy because they are strictly tumor specific and shared by many tumors of various histological types. A number of MAGE-A3 antigenic peptides presented by HLA class I molecules have been used in clinical trials, and regressions of melanoma metastasis have been observed. We report here the identification of a MAGE-A3 epitope, TQHFVQENYLEY, presented to CD4+ T lymphocytes by HLA-DP4 molecules, which are expressed in approximately 76% of Caucasians. This new epitope may be useful both for therapeutic vaccination and for the evaluation of the immune response in cancer patients. Interest ingly, the CD4+ T cells lysed HLA-DP4 tumor cells expressing MAGE-A3, indicating that this epitope, in contrast to other class-II MAGE-A3 epitopes, is presented at the surface of tumor cells. The study of this disparity in the presentation of two epitopes from the same protein may lead to a better understanding of the endogenous class II presentation pathway.

Animals↗

[Recurrent angioedema with gastroenteritis in blood and tissue eosinophilia].

A 23-year-old patient suffered from episodic angioedema of the face and neck, accompanied by diarrhea and abdominal pain. Additionally, the patient had bronchial asthma, recurrent nasal polyps and allergic rhinoconjunctivitis. Blood examination revealed leucocytosis with eosinophilia. Histological studies showed eosinophilic infiltrates in the skin and the gastrointestinal mucosa. Allergic food reactions and parasites were ruled out. With systemic corticosteroid treatment, the clinical symptoms and the eosinophilia disappeared. This case shows some parallels to previously described syndromes (eosinophilic gastroenteritis, Samter's syndrome, episodic angioedema with eosinophilia), but to the best of our knowledge this combination of symptoms has not yet been reported.

Adult↗

Clinical and prognostic relevance of serum S-100 beta protein in malignant melanoma.

To assess the clinical and prognostic relevance of serum S-100 beta in malignant melanoma serum levels of S-100 beta protein were measured in 84 patients with malignant melanoma. Using a cut-off value of 0.3 microgram/L the sensitivity was 0% (none of 36) in patients with stage II, 31% (four of 13) in patients with stage III and 69% (24 of 35) in patients with stage IV. In the reference group serum S-100 beta was below 0.3 microgram/L in all cases (specificity = 100%). A significant correlation existed between serum S-100 beta values and clinical staging as well as survival. In patients with distant metastases the serum concentration of S-100 beta protein correlated well with the number of affected organs. Serial measurement in these patients revealed that tumour progression was accompanied by rising S-100 beta values whereas declining values could only be revealed in one patient with a dramatic clinical response to therapy. Our results suggest that serum S-100 beta determination is a useful marker for the evaluation of prognosis in patients with metastatic malignant melanoma and should be included in the clinical staging.

Adult↗

Systemic corticosteroids are important in the treatment of Fournier's gangrene: a case report.

Fournier's gangrene represents an acute severe necrotizing inflammatory process affecting the scrotum and penis. It has an associated mortality of 30-50%. In most cases, aetiological factors can be identified, such as diabetes mellitus, chronic alcoholism and perianal, perirectal or periurethral infection. The disease is characterized by a polybacterial infection, and the classic treatment includes surgical removal of the necrotic tissue and the use of broad-spectrum antibiotics. We report a case of Fournier's gangrene, histologically characterized by a necrotizing vasculitis, in which surgical resection of the necrotic tissue and antibiotic treatment failed to halt progression of the disease, whereas complete remission was achieved by high-dose corticosteroid therapy. This suggests that Fournier's gangrene is related to some form of localized vasculitis, and represents a local Shwartzman phenomenon.

Anti-Inflammatory Agents↗

Influence of various cytokines on the interleukin-2-dependent lysis of melanoma cells in vitro.

To obtain information about useful combinations of various cytokines in melanoma therapy, we studied the influence of interleukin-2 (IL-2) in combination with interferon-alpha (IFN-alpha), IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) on the lytic activity of IL-2-stimulated cells in vitro. Peripheral mononuclear cells (PMC) were incubated for 4 days with various combinations of cytokines and used as effector cells. Two different melanoma cell lines (M19 and M26) were used as target cells. The lytic activity of stimulated PMC was determined using a modified hexosaminidase assay. IL-2 was mainly responsible for the lytic activity of the effector cells in a dose-dependent manner. IFN-alpha, IFN-gamma and TNF-alpha did not enhance lytic activity with an optimal IL-2 dose (50 IU/ml IL-2). Using a suboptimal IL-2 dose (5 IU/ml), they increased cytotoxicity. The specific lysis of M19 cells was significantly increased by pretreatment of the cells with 5 IU/ml IFN-alpha together with 50 IU/ml TNF-alpha (t-test, P < or = 0.001), while the specific lysis of M26 cells was increased by pretreatment with 5 IU/ml IFN-gamma. We conclude that the lysis of melanoma cells by cytotoxic cells in vitro can be enhanced by various cytokines. The optimal cytokine combination differed for the two melanoma cell lines tested.

Cytokines↗