Development and implementation of delivery and quality control system for cellular therapies: experience in 500 patients.
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Blood Transfusion, Autologous↗
Biomedical subjects
M Osband
Publications and source records attributed to M Osband.
Adoptive immunotherapy of hormone-refractory, stage D2 prostate cancer using ex vivo activated autologous T cells (autolymphocyte therapy): results from a pilot study.
There is no effective therapy available for stage D2 prostate cancer once patients become refractory to hormonal therapy. In a pilot study, we treated 17 patients with hormone-refractory stage D2 prostate cancer using autolymphocyte therapy, an outpatient form of adoptive immunotherapy in which patients are treated with autologous T cells that have been activated ex vivo. Feasibility and safety were documented. Transient PSA reductions up to 66% were noted, suggesting biological activity. Further studies to test the safety and efficacy of autolymphocyte therapy in the treatment of prostate cancer are warranted.
Aged↗
Autolymphocyte therapy.
Autolymphocyte therapy is medical treatment based upon the infusion of autologous lymphocytes that have been immunized or modulated in vitro. These infused cells subsequently provoke fundamental immunobiologic changes in the host. We suggest that autolymphocyte therapy might be a useful approach in the treatment and prophylaxis of several diseases.
Autoimmune Diseases↗
Phenotypic and functional evaluation of suppressor cells in normal pregnancy and in chronic aborters.
To evaluate the potential role of immunoregulatory cells modulating the maternal immunologic response during pregnancy, we carried out phenotypic and functional studies in patients with normal obstetrical histories during each trimester and in patients with chronic idiopathic spontaneous abortions. Using monoclonal antibodies (Ortho), total numbers of T cells (T3+) and T4+ cells progressively increased during pregnancy (compared to nonpregnant controls) and then declined in the third trimester. Increased percentages of T8+, T10+, and Ia+ cells were found in the third trimester. The relative decline in numbers of T4+ cells, with increased numbers of T8+ cells, led to a significantly reduced T4/T8 ratio in the third trimester. Histamine receptors on T cells were quantitated by an immunofluorescent technique. Significantly reduced numbers of H1-type receptors were noted during the second trimester of pregnancy and this was associated with a decreased H1/H2 ratio. Functionally, histamine-induced suppression was measured in a lymphocyte proliferation assay. Patients in the first and second trimester of pregnancy had greater histamine-induced suppression of phytohemagglutinin (PHA)-stimulated proliferation at high concentrations of histamine (10(-3) to 10(-7)) but less suppression at the lower concentrations (10(-9) to 10(-11) M), compared to nonpregnant controls. In contrast, patients studied in the third trimester failed to respond to any concentration of histamine. MLC-induced suppressor activity was generated by incubating the maternal cells with either paternal or third-party mononuclear cells for 2 or 6 days and assaying the cell-free supernatant for its suppressive effects on PHA-stimulated proliferation. Maternal responses to paternal cells did not result in significant suppression in 2-day supernatants during any trimester but by 6 days the suppressive activity was equivalent to non-pregnant controls in patients during the first and second trimester. Maternal responses to third party cells was greater during the second trimester than either the first or third trimesters in both 2- and 6-day supernatants. Patients with histories of chronic idiopathic spontaneous abortions, who were not pregnant at the time of study, exhibited normal numbers of T-cell subsets and T4/T8 ratios. Numbers of both H1 and H2 receptor bearing T cells were proportionally reduced, resulting in a normal H1/H2 ratio. Despite having decreased numbers of H1 and H2 receptor bearing cells, histamine-induced suppression of PHA-stimulated proliferation was comparable to nonpregnant controls over the concentration range (10(-3) to 10(-11) M) employed.(ABSTRACT TRUNCATED AT 400 WORDS)
Abortion, Habitual↗
The effect of the plant cell inhibitor propachlor (alpha-chloro-N-isopropyl-acetanilide) on the cell cycle of L1210 cells as evaluated by flow cytometry.
Previously it was reported that the herbicide propachlor (alpha-chloro-N-isopropyl-acetanilide) has a strong inhibitory effect on the proliferation of L1210 mouse leukemia cells. It is now demonstrated that propachlor treatment causes L1210 cells to accumulate in the G1 phase as determined by flow cytometric analysis. This effect of propachlor is dose-dependent with more than 90% of G1 cells accumulating at 10 microM. Kinetic experiments demonstrated that the accumulation of cells in G1 starts in about 10 hours, and increased for up to about 44 hours of incubation with 10 microM propachlor. Treated cells can be revised to a normal DNA distribution by removing propachlor.
Acetanilides↗
Helper cell function of Leukemic Leu-2a+, histamine receptor+, T gamma lymphocytes.
Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were found to have the surface phenotype Leu-1+, Leu-2a+, Leu-3a-, sheep erythrocyte rosette+, IgGFc receptor+. The cells also bore a receptor for histamine inhibitable by cimetidine (H-2). The clonal nature of the proliferation was documented by the presence of a consistent marker chromosome (22-trisomy) in metaphases elicited by culture with T cell growth factors. Although the surface phenotype suggested that these cells might function as suppressor lymphocytes, they had an enhancing effect on the pokeweed- mitogen- (PWM) driven generation of plasma cells and reverse hemolytic plaque-forming cells in vitro. This helper activity was modified neither by irradiation of the leukemic cells nor by removal of a minor population of Leu-3a+ cells, suggesting that the effects were attributable to the CLL cells themselves. In addition to these functions, the CLL cells were active in antibody-dependent cellular cytotoxicity (ADCC) assays in association with expression of Fc receptors for IgG. The ADCC was diminished when a transient loss of the Fc receptor expression was observed. No activity in natural killer cell assays employing K-562 cells or herpes simplex virus- (HSV) infected cells as targets could be attributed to the leukemic clone. These studies indicate that the cell surface phenotype, as defined by monoclonal antibodies, may not always predict the functional state of a particular cell, and suggest that within the Leu-2a+ (TH-2+) population of human lymphocytes, some helper as well as suppressor/cytotoxic cells are to be found.
Antibody-Dependent Cell Cytotoxicity↗
Clinical utility of leukemia cell terminal transferase measurements.
Interest in the DNA-synthetic enzyme terminal deoxynucleotidyl transferase (TdT) has developed from two sets of observations: first, in normal animals, it occurs only in immature thymic lymphocytes and in a subpopulation of bone marrow lymphocytes; second, it is present in the blast cells of almost all patients with acute lymphoblastic leukemia. A prospective trial to evaluate blast cell TdT as a predictor of responsiveness to vincristine and prednisone in 30 Philadelphia chromosome-positive patients with blastic chronic myelogenous leukemia was undertaken. Eleven of 16 TdT-positive patients responded, whereas only one of 14 TdT-negative patients showed improvement. Among TdT-positive patients under the age of 50 years, the response rate was 78%. Enzyme-negative patients under the age of 50 had an 11% response rate. Blast cell morphology (i.e., lymphoblastic versus myeloblastic) had no significant correlation with either responsiveness or TdT activity. These results suggest that blast cell TdT activity may identify leukemic patients who are likely to respond to vincristine and prednisone irrespective of their conventional classification.
Adolescent↗
Solubilization, separation, and partial characterization of histamine H1 and H2 receptors from calf thymocyte membranes.
Histamine membrane receptors are defined as either H1 (blocked by diphenhydramine-like antagonists) or H2 (blocked by cimetidine-like agents). We now report the solubilization, separation, and partial characterization of specific H1 and H2 membrane receptors from calf thymocytes. Membrane fragments were incubated with [3H]histamine either alone or with unlabeled histamine, diphenhydramine, or cimetidine. Maximal specific binding occurred with incubation at 37 degrees C for 2 h at a concentration of 5 x 10(-6) M [3H]histamine. Labeled receptors were solubilized from membranes with 0.3 M KCl and 1% Nonidet 40. Chromatography of the solubilized labeled receptors on ion exchange columns revealed two classes of receptor. One class bound to DEAE-cellulose and eluted as a sharp peak at 0.15 M NaCl/Pi. The other bound to phosphocellulose and eluted as a sharp peak at 0.55 M NaCl/Pi. Initial incubation of the membranes in the presence of the H1 receptor antagonist diphenhydramine virtually abolished the DEAE-cellulose peak, while incubation with cimetidine, the H2 receptor antagonist, blocked the phosphocellulose peak. We conclude that H1 and H2 histamine receptors are physically separable and can be defined by their ability to bind to either DEAE-cellulose or phosphocellulose.
Animals↗
The control of autoreactivity. I. Lack of autoreactivity in murine spleens is due to concomitant presence of suppressor and autocytotoxic lymphocytes.
To determine if autocytotoxic lymphocytes were naturally occurring in murine spleens, C57BL/6 spleen cells were fractionated on discontinuous BSA gradients. Autocytotoxicity was assessed in vitro (cytotoxicity of C57BL/6 fibroblasts) and in vivo (splenomegaly and popliteal node enlargement in C57BL/6 mice). A medium density subpopulation of lymphocytes was shown to be autocytotoxic and to be similar to autoreactive lymphocytes produced by the in vitro "sensitization" of splenic lymphocytes on syngeneic fibroblasts monolayers. The naturally occurring autocytotoxic lymphocytes express no detectable theta antigen, did not adhere to nylon, but did have an Fc receptor. In recombination experiments, BSA-fractionated lymphocytes were incubated with autocytotoxic and "sensitized" lymphocytes. A light density subpopulation was shown to suppress both autoreactive lymphocyte subpopulations at a 1:50 ratio. The suppressor cells were nylon nonadherent T lymphocytes. The lack of autoreactivity of unfractionated murine spleen cells is due to the concomitant presence of autocytotoxic and suppressor lymphocytes. If suppressor lymphocytes are selectively removed in vitro, the reactivity of autocytotoxic lymphocytes can be detected.
Animals↗
The rapid diagnosis of infectious mononucleosis using an ELISA that detects IgM antibody to a peptide component of Epstein-Barr virus nuclear antigen.
An enzyme-linked immunosorbent assay (ELISA) that detects IgM antibody to a peptide component of the Epstein-Barr virus (EBV) nuclear antigen (EBNA-1) was compared with a conventional rapid heterophil antibody method for the rapid diagnosis of infectious mononucleosis. Discrepancies between the two methods were further analyzed using an indirect immunofluorescence assay to detect antibodies to EBV antigens. We evaluated 298 cases of suspected infectious mononucleosis. The ELISA was very sensitive (98.7%) and able to detect some cases (seven (9%) of 75 confirmed positives) that were negative by the rapid heterophil antibody test, but confirmed by immunofluorescence. However, approximately 17% of all positive tests could not be confirmed by EBV-specific immunofluorescence; thus, the overall positive predictive value was 83%; negative predictive value was 99.5%; and specificity was 93%. The high rate of false-positive tests makes this rapid ELISA unsuitable for the diagnosis of infectious mononucleosis.
Adolescent↗