1/54. Polymorphic light eruption occurring in common variable hypogammaglobulinaemia, and resolving with intravenous immunoglobulin therapy.A 55-year-old woman with a past history of lower respiratory tract infections presented with a photosensitive eruption. Polymorphic light eruption (PLE) was diagnosed on the basis of the temporal relationship to sun exposure and the diagnosis was supported by positive monochromator irradiation tests in the ultraviolet A wavelength spectrum. Investigation of the patient's immune status identified low levels of all immunoglobulin (Ig) subtypes consistent with common variable hypogammaglobulinaemia. Intravenous Ig replacement therapy, instituted to minimize risks from bacterial infections, was commenced and over the ensuing months resulted in a complete resolution of the PLE. PLE is considered to represent a type IV hypersensitivity reaction directed against a cutaneous autoantigen induced by exposure to ultraviolet light. In PLE, nonspecific immunomodulatory mechanisms of intravenous Ig may be active, such as a reduction in the synthesis of cytokines and a blockage of the IgG Fc receptors on macrophages.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/54. phenytoin sensitivity in a case of phenytoin-associated Hodgkin's disease.The case of a patient who developed Hodgkin's disease three years after commencement of therapy with phenytoin is presented. Humoral and cellular immunological capacity were significantly depressed. phenytoin caused a striking increase in dna synthesis when lymphocytes were culture in the presence of this drug, in contrast to significant inhibition in the lymphocytes of control subjects. These findings are consistent with the hypothesis that both chronic antigenic stimulation and immunosuppression by phenytoin and involved in the induction of lymphoma.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/54. Analysis of a chronic myelogenous leukemia patient vaccinated with leukemic dendritic cells following autologous peripheral blood stem cell transplantation.dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Ph1 , and to possess the morphologic and phenotypic characteristics of mature DCs. These cells could also elicit antigen specific immune responses, including a vigorous cytotoxicity specific to CML cells. In the clinical experiment, we obtained evidence that infused leukemic DCs could induce T cell clones expressing the same T cell receptor usage as a cytotoxic T cell line, suggesting that the immune repertoire includes tumor-reactive T cells. These cytotoxic T lymphocytes are activated in vivo. The vaccination of leukemic DC caused a decrease in the number of Ph1 cells in the peripheral blood and bone marrow. These results indicate that the activity is an immunologically mediated phenomenon and vaccination therapy with leukemic DC following autologous PBSCT may be effective in treating CML.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
4/54. Dendritic cell immunotherapy induces antitumour response in parathyroid carcinoma and neuroendocrine pancreas carcinoma.Parathyroid carcinomas and neuroendocrine carcinomas of the pancreas are rare malignancies in humans. Because of their low radio- and chemosensibility, they fail to respond to conventional therapy. We therefore tested a dendritic cell immunotherapy in an attempt to control the tumour growth in two patients. Studies on mice and humans have demonstrated the potent capacity of dendritic cells to induce specific antitumour immunity. Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin 4 and tumour necrosis factor alpha. dendritic cells were either loaded with parathyroid hormone (PTH) or with (pancreas) tumour-derived lysate (TL), respectively, and were delivered by subcutaneous injections. All immunizations were well tolerated with no side effects, and were administered on an outpatient basis. After repeated vaccinations, specific in vivo immune response was demonstrated by positive delayed-type hypersensitivity (DTH) toward PTH or TL, demonstrating the efficient generation of antigen-specific memory T-cells. DTH reactivity was accompanied by a significant decrease of tumour markers in both patients. This approach might be generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/54. Clonal expansion of Melan A-specific cytotoxic T lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides.peptides derived from human tumor antigens have been used in a number of clinical trials to induce specific immune responses against autologous tumors in cancer patients. Although favorable clinical results were observed in single patients, immune responses correlating with tumor regression were either not detected or in case of responses, the T-cell specificity was difficult to demonstrate. In this study, we analyzed antigen-specific T-cell responses induced in the skin and in peripheral blood lymphocytes (PBL) in an HLA-A2-positive melanoma patient. The patient showed major regression of metastatic melanoma under continued immunization with peptides derived from the melanocyte differentiation antigens Melan A/MART-1, tyrosinase and gp100/Pmel17. Based on the identification of different T-cell receptor (TCR) families reactive with Melan A/MART-1, we have demonstrated that i.d. immunization with peptides alone leads to oligoclonal expansion of Melan A/MART-1-specific cytotoxic T lymphocytes (CTL), detectable in local delayed-type hypersensitivity (DTH) reactions and PBL. A monoclonal expansion of a Melan A/MART-1-specific TCR VB 16 CTL was reproducibly observed after in vitro stimulation with Melan A/MART-1 peptides. The same TCR VB 16 CTL clone was detected in skin biopsies taken from vitiligo areas. Our findings provide strong evidence for the effective induction of specific T-cell responses to Melan A/MART-1 by i.d. immunization with peptide alone, which accounts for dermal depigmentation, specific cytotoxicity against Melan A/MART-1-expressing melanoma cells and clinical tumor regression.- - - - - - - - - - ranking = 3keywords = antigen (Clic here for more details about this article) |
6/54. Regression of cutaneous neoplasms following delayed-type hypersensitivity challenge reactions to microbial antigens or lymphokines.Induction of delayed-type hypersensitivity challenge reactions to microbial antigens at sites of neoplasms involving the skin resulted in regression of mycosis fungoides, reticulum cell sarcoma, superficial basal cell carcinoma and adenocarcinoma of the breast. Similar reactions induced by lymphokine preparations also resulted in regression of lesions of mycosis fungoides and superficial basal cell carcinoma. The role of the large monomuclear cells in the inflammatory infiltrate of the delayed hypersensitivity reaction in eliciting the tumor regression is discussed. It is proposed that these large mononuclear cells represent the effectors in a primitive surveillance mechanism for neoplastic cells.- - - - - - - - - - ranking = 5keywords = antigen (Clic here for more details about this article) |
7/54. Loss of tolerance to a maternal kidney transplant is selective for HLA class II: evidence from trans-vivo DTH and alloantibody analysis.We studied late graft rejection in a patient who had received a kidney transplant 9-10 years earlier from his mother and who had been off all immunosuppressive drugs for 7 years at the time of graft rejection onset. The mother differed for one HLA-A (A3) and one HLA-B (B62) antigen but had only a subtype mismatch at the HLA-DR beta 1 locus (donor: DR beta 1*1104; recipient: DR beta 1*1102). A gradual rise in serum creatinine from 1.8 to 2.0 mg/dl at year 9 prompted a biopsy, which was negative for rejection (focal infiltrates but no tubulitis). Ten months later the patient's creatinine had risen to > 3.4 mg/dl, and a second biopsy revealed extensive tubulitis, cellular rejection, and glomerular sclerosis. Sonicates of donor leukocytes triggered no delayed-type hypersensitivity (DTH) response above background (PBMC only) in the patient's peripheral blood leukocytes obtained prior to year 9. A gradual recovery of antidonor DTH response between year 9 and 10 closely paralleled the change from tolerant to rejection status. Antidonor antibody was also undetectable in serum prior to year 9, but a donor-reactive antibody did develop at year 10.2 shortly after the peak of DTH response. The serum level of soluble donor HLA class I B62 antigen rose > 10-fold over prerejection level at the time of the biopsy-proven rejection, suggesting a possible trigger for both the cellular and humoral immune response. Nonetheless, we found no evidence for the development of humoral or cellular immunity to maternal HLA class I. Instead, DTH analysis of memory T cells of the patient obtained after rejection showed that a single maternal HLA DR beta 1*1104 allopeptide, differing by two amino acids in sequence from the peptide of the recipient (DR beta 1*1102), stimulated a strong memory DTH response. Similarly, we found an anti-HLA class II donor-specific antibody in serum that appeared to be crossreactive with DR beta 1*1104 and DR beta 1*1101 but not with the recipient DR beta 1*1102 antigen. The data support the idea of a profound unresponsive state at both the cellular (DTH) and humoral level toward maternal HLA class I antigens that was not reversed even during late cellular rejection, despite the release of high levels of soluble HLA class I. Furthermore, the data suggest that DTH recovery was a close correlate of the onset of rejection and this "indirect" alloresponse, like the anti-donor alloantibody response that followed, was directed not to noninherited maternal HLA-A,B antigens but to the maternal HLA DR beta 1*1104 subtype.- - - - - - - - - - ranking = 5keywords = antigen (Clic here for more details about this article) |
8/54. erythema induratum in a patient with active tuberculosis of the axillary lymph node: IFN-gamma release of specific T cells.A 57-year-old woman with tender nodular lesions on her legs, arms, buttocks and face is reported as a case of erythema induratum (EI) with active tuberculosis of axillary lymph nodes. Both skin nodular lesions and lymph nodes responded positively to antituberculous therapy. The patient's peripheral blood mononuclear cells showed a high proliferation and produced interferon-gamma (IFN-gamma) in response to purified protein derivative (PPD). These findings indicate the possibility that PPD-specific T cells, capable of producing IFN-gamma, are likely to be involved in the formation of EI as a type of delayed-type hypersensitivity response to mycobacterial antigens at the site of skin lesions.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/54. Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma.OBJECTIVE: Metastatic neuroendocrine carcinomas of the pancreas frequently fail to respond to conventional therapies, including radiation and chemotherapy. We therefore tested a dendritic cell-based immunotherapy in an attempt to eradicate residual tumour masses in a patient suffering from a metastatic insulin-producing pancreatic carcinoma. DESIGN: Autologous dendritic cells (DCs) were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumour necrosis factor alpha. DCs were loaded with tumour-derived lysate (TL), and were delivered by subcutaneous injections in 4-week intervals. RESULTS: Three weeks after first treatment, the patient developed a strong delayed-type hypersensitivity (DTH) skin reaction with an erythema and induration after the challenge with TL-pulsed DCs, which indicates the efficient generation of antigen-specific memory T-cells. Immunohistochemical analysis of skin biopsy demonstrated a strong perivascular and epidermal infiltration by T-helper (CD4 positive) and cytotoxic T cells (CD8 positive). Stimulation with TL revealed a dose-dependent T-cell proliferation with a stimulation index of 1.1-5.7 compared to 1.1-1.4 before vaccination (P < 0.01). Most strikingly, DC-based vaccination was accompanied by a steady decrease of the tumour marker chromogranin a from 2.93 umol/l initially to below the detection limit of 0.15 umol/l within 9 months of therapy. The ultrasound examination revealed a tumour regression of the metastasis in the right lobe of the liver. CONCLUSIONS: Our data indicate that vaccination with tumour lysate-pulsed DCs induced a significant antitumour immune response in a neuroendocrine carcinoma of the pancreas. This approach represents an alternative strategy for the treatment of advanced neuroendocrine carcinomas that are resistant to conventional therapy.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/54. Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.A human cancer vaccine composed of autologous tumor cells modified with the hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP vaccine could induce regression of established metastases. Ninety-seven patients (83 evaluable) with surgically incurable metastatic melanoma were treated with DNP vaccine preceded by low-dose cyclophosphamide. Tumor regression was assessed by standard criteria. The development of cell-mediated immunity to melanoma-associated antigens was measured by delayed-type hypersensitivity (DTH) testing before and after DNP vaccine treatment. survival analysis was performed by the Kaplan-Meier method. There were 11 antitumor responses: 2 complete, 4 partial and 5 mixed. Both complete responses and 2 of the 4 partial responses occurred in patients with lung metastases. Response durations were as follows: partial responses-5, 6, 8 and 47 months; and complete responses-12 and 29 months. Tumor regression required at least 4 months to become evident and in 2 cases maximum regression was not observed until 1 year after beginning treatment. patients who exhibited tumor regression survived longer than those who did not (median survival times: responders, 21.4 months; non-responders, 8.7 months; p = 0.010). DTH to DNP-modified and unmodified autologous melanoma cells was induced in 87% and 42% of patients, respectively. The DTH response to unmodified cells was significantly associated with prolonged survival. Autologous DNP-modified melanoma vaccine can induce clinically meaningful regression of metastases and small lung metastases appear to be unusually sensitive. The development of DTH to unmodified, autologous tumor cells may be an important indicator of the vaccine's efficacy.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
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