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1.
Bone Marrow Transplant ; 47(12): 1513-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22580767

ABSTRACT

Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.


Subject(s)
Antilymphocyte Serum/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Cohort Studies , Female , Graft vs Host Disease/prevention & control , Humans , Male , Middle Aged , Myelodysplastic Syndromes/surgery , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Analysis , Tissue Donors , Transplantation, Homologous , Treatment Outcome , Unrelated Donors
2.
Vaccine ; 24(9): 1282-90, 2006 Feb 27.
Article in English | MEDLINE | ID: mdl-16225969

ABSTRACT

A needle-free method based on transcutaneous electroporation is described for delivering peptide vaccines. The K(b)-binding OVA-peptide SIINFEKL was used as an example to induce the peptide-specific cytotoxic T-lymphocytes (CTL) response in mice. A saturated anionic lipid was added during electroporation, and post-pulse electro-osmosis was applied to enhance the vaccine delivery. Electroporation was found to stimulate the exodus of Langerhans cells (LC) from the skin. The peptide transported into and through murine skin was measured using a Franz diffusion apparatus. Most peptide was retained in the skin rather than passing through the skin in the process. The peptide was delivered to the dorsal skin of mice by in vivo electroporation. An electroporation-transportable oligonucleotide with CpG motif was used as adjuvant. The efficacy of peptide delivery was comparable to that of intradermally injected with Freund's complete adjuvant (FCA). Peptide-specific CTL response to the vaccine delivered by needle-free electroporation/electro-osmosis was equivalent to that delivered by intradermal injection, as determined by production of the peptide-specific IFN-gamma in ELISPOT assay.


Subject(s)
Electroporation , Immunization/methods , T-Lymphocytes, Cytotoxic/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Administration, Cutaneous , Animals , Cell Movement , Dendritic Cells/immunology , Female , Freund's Adjuvant/administration & dosage , Freund's Adjuvant/pharmacology , Injections, Intradermal , Interferon-gamma/biosynthesis , Mice , Mice, Inbred C57BL , Models, Animal , Oligodeoxyribonucleotides/administration & dosage , Oligodeoxyribonucleotides/pharmacology , Ovalbumin/administration & dosage , Ovalbumin/immunology , Peptide Fragments/administration & dosage , Peptide Fragments/immunology
3.
Int J Hyperthermia ; 18(6): 506-20, 2002.
Article in English | MEDLINE | ID: mdl-12537751

ABSTRACT

Heat shock proteins (hsps) can induce anti-cancer immune responses by targeting associated tumour antigens to the immune system. Hsps are not merely carriers of antigen but can also induce maturation of dendritic cells (DCs), resulting in a more efficient antigen presentation. However, improvement of hsp-based vaccines is still desirable if one is to realize their full therapeutic potential. Since the immune system consists of different elements functioning together in a highly integrated way, a combination therapy utilizing important immunomodulators together with hsp-based vaccination may improve therapeutic response. Hyperthermia has been shown to have important stimulatory effects on several cellular and organismal endpoints related to the immune system. This review highlights advantages and disadvantages of various ways of using stress proteins in cancer immunotherapy. It also overviews the interaction of hyperthermia with heat shock protein therapy and the related effects on the host's immune response.


Subject(s)
Heat-Shock Proteins/physiology , Hyperthermia, Induced , Immunotherapy , Neoplasms/therapy , Stress, Physiological/physiopathology , Animals , Antigen Presentation/immunology , Cancer Vaccines , Humans , Neoplasms/immunology , Neoplasms/physiopathology
4.
Parasitol Res ; 86(4): 311-7, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10780740

ABSTRACT

In vitro leucocyte proliferative responses to parasite antigens and to mitogens as well as lymphocyte sub-types were compared in guinea pigs with genetically determined differences in their ability to express protective immunity against Trichostronylus colubriformis infection. Proliferative responses to parasite antigens were greatest in high-responder (HR) animals, but cells from low-responder (LR) animals were generally more responsive to mitogens. However, HR circulating leucocytes were more responsive to the T-cell-dependent B-cell mitogen pokeweed mitogen (PWM), and the response of HR, but not LR, cells increased during primary infection with T. colubriformis. Flow cytometry revealed significantly greater numbers of circulating B-cells in HR animals and, as observed for responsiveness to PWM, the number of circulating B-cells increased in HR, but not LR, animals during primary infection with this parasite. These findings suggest a larger and more labile population of B-cells in HR guinea pigs.


Subject(s)
Guinea Pigs/immunology , Lymphocyte Activation/immunology , Lymphocyte Subsets/immunology , Rodent Diseases/immunology , Trichostrongylosis/veterinary , Trichostrongylus/immunology , Animals , Cells, Cultured , Female , Flow Cytometry/veterinary , Genetic Predisposition to Disease , Immunophenotyping/veterinary , Intestinal Diseases, Parasitic/genetics , Intestinal Diseases, Parasitic/immunology , Lymphocyte Activation/genetics , Male , Rodent Diseases/genetics , Rodent Diseases/parasitology , Trichostrongylosis/immunology
5.
Int J Parasitol ; 29(2): 255-61, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10221625

ABSTRACT

Antibody levels were compared in guinea pigs with genetically determined differences in their ability to generate protective immunity against the small-intestine nematode parasite Trichostrongylus colubriformis. Animals with the most effective immune response (high responders) developed significantly higher anti-T. colubriformis IgG1 antibody titres than low-responder animals. However, there were no significant differences between their IgG1 antibody responses to a systemically administered protein antigen (ovalbumin). High-titre anti-T. colubriformis serum from high-responder animals did not transfer significant passive protective immunity to low-responder recipients. It is suggested that anti-T. colubriformis IgG1 antibodies mediate the release of mast-cell and basophil products at the site of infection and thus contribute to the more effective immunity expressed by high-responder animals.


Subject(s)
Antibodies, Helminth/blood , Trichostrongylosis/immunology , Trichostrongylus/immunology , Animals , Antigens, Helminth/immunology , Guinea Pigs , Immunity, Innate , Immunization , Immunoglobulin Isotypes/blood , Ovalbumin/administration & dosage , Ovalbumin/immunology , Trichostrongylosis/parasitology
6.
Int J Parasitol ; 28(5): 761-5, 1998 May.
Article in English | MEDLINE | ID: mdl-9650056

ABSTRACT

Small intestine goblet cell numbers and the composition of their mucus were compared in guinea pigs with genetically determined differences in responsiveness to Trichostrongylus colubriformis infection. Prior to infection, no differences between high responder and low responder animals were detected. However, following primary infection with T. colubriformis, pronounced goblet cell hyperplasia developed and the proportion of sulphomucin in these cells increased. Both changes developed significantly earlier in high responder animals.


Subject(s)
Intestinal Mucosa/pathology , Trichostrongylosis/pathology , Animals , Disease Susceptibility , Feces/parasitology , Guinea Pigs , Host-Parasite Interactions , Intestinal Mucosa/chemistry , Intestinal Mucosa/parasitology , Mucins/analysis , Parasite Egg Count , Staining and Labeling , Time Factors , Trichostrongylosis/immunology , Trichostrongylosis/parasitology , Trichostrongylus/physiology
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