M. Blaese - Academia.edu (original) (raw)

Papers by M. Blaese

Human Gene Therapy, 1990

Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes w... more Lymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genes in vitro for long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes both in vitro and in vivo to determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (hADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periods in vivo and can continue to express the introduced genes.

Journal of Pediatric Gastroenterology and Nutrition, 2001

... Case Reports. Primary Sclerosing Cholangitis in Wiskott-Aldrich Syndrome. Kahn, Khalid; Sharp... more ... Case Reports. Primary Sclerosing Cholangitis in Wiskott-Aldrich Syndrome. Kahn, Khalid; Sharp, Harvey; Hunter, David*; Kerzner, Benny; Jessurun, Jose; Blaese, Michael§. Article Outline. Collapse Box Author Information. Departments ...

Protides of the Biological Fluids, 1972

Journal of immunology (Baltimore, Md. : 1950), 1984

Glucocorticosteroids (GCS) are in vitro polyclonal activators of immunoglobulin (Ig) production f... more Glucocorticosteroids (GCS) are in vitro polyclonal activators of immunoglobulin (Ig) production for human mononuclear cells (MC) from virtually all adult donors. However, GCS treatment of cord blood MC resulted in Ig production in only 12/41 samples. This GCS effect is T cell and monocyte dependent and is mediated in part by a soluble T cell replacing factor. The inconsistent response of cord MC could be due to either cellular or soluble factor differences from adults. In 11/12 samples tested, irradiated cord T cells did help adult B cells, but less than did irradiated allogeneic adult T cells. T cell suppression in cord samples is unlikely inasmuch as higher cord T cell numbers and proportions increased the number of responding cord samples. Cord monocytes function adequately, because monocytes supported GCS responses when cord non-T cells had sufficient T cell help. The T cell replacing factor was found in supernatants of unstimulated cord as well as in adult MC cultures, but was ...

New England Journal of Medicine, 1979

Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen bec... more Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen because it preferentially infects B lymphocytes and consequently activates them to produce immunoglobulins. When cultures of lymphocytes from patients with infectious mononucleosis were stimulated with polyclonal activators, unseparated cells failed to produce immunoglobulins, whereas purified B cells responded normally. Cocultures demonstrated profound suppressor T-cell activity in blood from patients with infectious mononucleosis. Early in this disease, circulating immunoglobulin-secreting cells were elevated, but during the second week their number was strikingly depressed. These data indicate that during infectious mononucleosis, EBV causes polyclonal activation of B cells, reflected by hypergammaglobulinemia and increased circulating immunoglobulin-secreting cells. Next, suppressor T cells become activated and inhibit further B-cell activation. Thus, activation of suppressor T cells in infectious mononucleosis provides a unique additional mechanism of host defense because these T cells inhibit the activation and proliferation of an important target of the causative virus.

Neurosurgical FOCUS, 2000

The authors investigated immunogene therapy for malignant glioma to determine whether its therape... more The authors investigated immunogene therapy for malignant glioma to determine whether its therapeutic efficacy could be improved. Four groups of 203-glioma-bearing mice were treated with injections of phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector DFG-interleukin (IL)-12, and SFV-IL12, respectively. The results indicated that therapeutic immunization with SFV-IL12 prolonged the survival of mice with established tumors. Semliki Forest virus induces apoptotic death to glioma cells, which facilitates the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. Immunogene therapy with IL-12 via SFV may be an excellent candidate for the development of new cancer vaccines.

Genomics, 1988

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive genetic disease in which the molecula... more The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive genetic disease in which the molecular defect is unknown. In 15 families with WAS, seven restriction fragment length polymorphic loci from the X chromosome were used to map the disease locus. Of the eight intervals studied, the likelihood of the WAS gene lying between DXS7 (Xp11.3) and DXS14 (Xp11) was at least 128 times higher than that for any other interval. The most likely gene order is DXS84-OTC-DXS7-WAS-DXS14-DXS1-PGK-DXYS1. Close genetic linkage to DXS7 and DXS14 permits accurate prenatal diagnosis and carrier detection with greater than 98% confidence in fully informative WAS families.

Cancer, 1980

Hodgkin's disease, nodular sclerosing, developed in a 16-year-old man with the Wiskott-Al... more Hodgkin's disease, nodular sclerosing, developed in a 16-year-old man with the Wiskott-Aldrich syndrome. Two brothers and two nephews had documented Wiskott-Aldrich syndrome and had died of infectious complications in childhood. While the patient reported here had lifelong thrombocytopenia and recurrent upper respiratory infections, he had no severe infection prior to the development of Hodgkin's disease. Skin test sensitization with dinitrochlorobenzene was unsuccessful. No antibodies were found after immunization with pneumococcal polysaccharides. Platelet aggregation studies were abnormal in the patient, his mother, and one of his nephews. A complete response of short duration occurred after treatment with nitrogen mustard, vincristine, procarbazine, and prednisone. On recurrence, he proved unresponsive to further chemotherapy or radiation therapy. Infection with four different fungi was found at autopsy. This patient is the third recorded case of Hodgkin's disease associated with the Wiskott-Aldrich syndrome.

Cancer gene therapy, 1995

1. Cancer Gene Ther. 1995 Dec;2(4):291-7. Vectors in cancer therapy: how will they deliver? Blaes... more 1. Cancer Gene Ther. 1995 Dec;2(4):291-7. Vectors in cancer therapy: how will they deliver? Blaese M, Blankenstein T, Brenner M, Cohen-Haguenauer O, Gansbacher B, Russell S, Sorrentino B, Velu T. Division of Bone Marrow Transplantation, St. ...

Journal of immunology (Baltimore, Md. : 1950), 1972

ABSTRACT

Current Protocols in Immunology, 2001

The enzyme-linked immunosorbent assay (ELISA) is a simple, specific, highly reproducible, and non... more The enzyme-linked immunosorbent assay (ELISA) is a simple, specific, highly reproducible, and nonradioactive method for measuring immunoglobulin levels in cell culture supernatants and other biologic fluids. It can be used to measure the common immunoglobulin classes (IgG, IgM, and IgA) as described in the basic protocol, as well as classes and subclasses found in low levels in these fluids (IgG4 and IgE), as detailed in the alternate protocols.

Clinical Immunology and Immunopathology, 1984

Expression of DR antigen on cord blood (neonatal) human monocytes using complement-mediated cytot... more Expression of DR antigen on cord blood (neonatal) human monocytes using complement-mediated cytotoxicity with anti-DR alloantisera and fluorescent-activated cell sorting (FACS) utilizing a battery of anti-DR mouse monoclonal antibodies was assessed. Forty preparations of neonatal cord blood monocytes were purified by adherence and elution from plastic petri dishes: lymphocyte contamination was <5% as indicated by esterase and peroxidase stains and cell sizing. By cytotoxicity tests 22 + 5.5% LSD) of neonatal monocytes expressed DR compared to its expression on 78.6 k 3. I% of adult monocytes. By FACS analysis, the frequency of DR expression on neonatal monocytes was 19-33s compared to 7l-82% for adult monocytes. Incubation of neonatal monocytes with concanavalin A (Con A) or phytohemagglutinin (PHAJ-stimulated human peripheral blood mononuclear cell culture supernatants (lymphokine) or recombinant interferon-u (IFN-(r) increased the expression of DR antigens in a dose-and time-dependent manner. A Con A-supplemented culture supernatant of unstimulated peripheral blood mononuclear cells had no effect on DR expression. Neonatal monocytes that were pretreated with anti-DR and complement in order to remove DR-positive cells were induced to express DR antigen after 2 days in culture with lymphokine. Thus DRnegative neonatal monocytes can be induced to express DR antigen. These results suggest a correctable maturational deficiency of neonatal monocytes. The inducibility of DR antigen expression by lymphokines and recombinant IFN-a suggests that they play an important role in the regulation of immune responses.

Human Gene Therapy, 1996

Tumor cells genetically modified to express immunostimulatory molecules can produce high levels o... more Tumor cells genetically modified to express immunostimulatory molecules can produce high levels of antitumor immunity in rodent models. Although a number of clinical trials are currently in progress to assess the value of the approach in human disease, almost all require ex vivo transduction of cultured tumor cells with retroviral vectors. This process is not feasible for many human malignancies, hampering clinical evaluation of the approach. We have used an E1a,1b/E3 deletion mutant of adenovirus containing either the lacZ or the human interleukin-2 (IL-2) gene to transduce human neuroblastoma cells. This vector transduces fresh neuroblastoma cells and neuroblastoma cell lines with an efficiency of 80-90%, compared to an efficiency of 0-14% obtained with retroviral vectors. Cells transduced with the IL-2 adenovector produce up to 12,000 pg of IL-2/10(6) cells/24 hr. IL-2 adenovector-transduced neuroblasts are immunostimulatory; when they are cultured with patient lymphocytes, they increase the proportion of DR+ T cells and generate major histocompatibility complex (MHC) unrestricted cytotoxic effector cells active against parental (nontransduced) tumor cells. We conclude that IL-2 adenovector can be used to transduce freshly isolated human tumor cells efficiently, which will then produce immunomodulatory quantities of the cytokine. The use of adenoviral rather than retroviral vectors facilitates preparation of human tumor &amp;quot;vaccines&amp;quot; and these vectors are now being used in our clinical study of neuroblastoma patients.

Human Gene Therapy, 1992

When tumor is resected from patients as part of the natural course of their treatment, an attempt... more When tumor is resected from patients as part of the natural course of their treatment, an attempt will be made to establish a tissue culture line of the tumor. The gene coding for tumor necrosis factor will be introduced into these tumor cells and the integration and expression of this gene will be tested. Patients will become eligible for this study only if they develop metastatic cancer that has failed all standard effective treatment and have no other effective treatment options available to them. Tumor cells will be injected intradermally and subcutaneously into the thigh of these patients. The amount of tumor injected will be less than 1/50th the total tumor burden of the patient. In previous studies we have shown that these gene-modified tumor cells are more immunogenic than the native unaltered tumor. Attempts will then be made to grow immune lymphocytes either from the tumor site or from the draining lymph nodes of these patients in order to use these lymphocytes for adoptive immunotherapy as detailed in previous protocols. The direct effect of the immunization with these immunogenic tumor cells will also be measured by assessing the impact on established tumor at other sites. Fifty patients receiving tumor inoculation will be included in this study.

European Journal of Cancer, 1995

Cancer Gene Therapy, 2001

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant br... more Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.

Annals of Surgery, 1993

The authors sought to develop new treatments for patients with cancer based on the genetic modifi... more The authors sought to develop new treatments for patients with cancer based on the genetic modification of immune lymphocytes and tumor cells designed to increase the host immune reaction against growing cancers.

Annals of the New York Academy of Sciences, 1987

... Genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase: Overview. ge... more ... Genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase: Overview. genetic heterogeneity and therapy. Birth Defects 19 73-8 I. ADRIAN, GS, DA WIGINTON, & JJ HUTTON. 1984. ... 12 1015-1024. ADRIAN, GS, DA WIGINTON & JJ HUTTON. 1984. ...