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L Vaickus

Publications and source records attributed to L Vaickus.

28 records · Page 2Linked to original sources
PubMed1991

Overview of monoclonal antibodies in the diagnosis and therapy of cancer.

Monoclonal antibodies initially offered the promise of a cure for cancer as "magic bullets" but this hope was quickly diminished as the complexities of the host-tumor relationship were realized. We have acquired a tremendous amount of practical experience since the first cancer patient was treated with a MAb nearly 10 years ago. This experience, combined with recent advances in recombinant DNA technology, has endowed us with a rich variety of opportunities to exploit in the diagnosis and treatment of malignancies. If recent preclinical research studies are clinically applicable and the antitumor responses seen in initial clinical trials can be optimized and confirmed, the next decade will likely be host to remarkable advances in the diagnosis and treatment of cancer with MAbs.

Animals↗
PubMed1990

Interferon gamma augments Lym-1-dependent, granulocyte-mediated tumor cell lysis.

Lym-1 is a therapeutically promising IgG2a monoclonal antibody (MoAb) that reacts with variant class II molecules expressed on B-lineage malignancies. To optimize antitumor immunotherapy with Lym-1, we determined whether granulocytes could participate in tumor lysis mediated by Lym-1 and whether recombinant interferon gamma (IFN-gamma) could influence this reaction. Granulocytes had minimal activity in mediating Lym-1 antibody-dependent cellular cytotoxicity (ADCC) compared with peripheral blood mononuclear cells (PBMC). However, IFN-gamma markedly augmented and occasionally induced granulocyte Lym-1 ADCC in a dose-dependent fashion (optimal 100 U/mL). Granulocytes primed with IFN-gamma for 24 hours displayed greatly increased ADCC in the absence of further IFN-gamma exposure. In most individuals, IFN-gamma also enhanced PBMC Lym-1 ADCC. Interferon alfa (IFN-alpha), although able to enhance PBMC-mediated Lym-1 ADCC and non-ADCC lysis, had no effect on granulocyte activity. Lym-1 ADCC involved an interaction between Fc receptor-bearing granulocytes and Lym-1 antigen positive targets based on the following: (1) The reaction was Lym-1 dose-dependent with cytotoxicity detectable at concentrations as low as 0.5 microgram/mL. (2) An irrelevant, isotype-matched MoAb (UPC-10) was unable to mediate ADCC. (3) In the absence of Lym-1, granulocytes--with or without IFN-gamma--displayed no intrinsic tumor lytic ability. Conversely, without granulocytes, Lym-1 or Lym-1 plus IFN-gamma had no effect. (4) Protein A, which binds avidly to Lym-1, inhibited the reaction 95%. (5) IFN-gamma induced granulocyte expression of CD64, the IgG Fc receptor that binds murine IgG2a MoAbs. (6) Of nine malignant human cell lines, only the three that moderately or strongly expressed the Lym-1 antigen were consistently lysed. Preclinical studies such as these may provide a rational basis for designing clinical trials with Lym-1 in combination with IFN-gamma.

Antibodies, Monoclonal↗
PubMed1990

Antibody-dependent, cell-mediated cytotoxicity by an anti-class II murine monoclonal antibody: effects of recombinant interleukin 2 on human effector cell lysis of human B-cell tumors.

Lym-1 is an IgG2a murine monoclonal antibody that reacts with variant Class II molecules expressed on B-cell malignancies. Lym-1 was shown to mediate antibody-dependent cellular cytotoxicity (ADCC) of human effector cells against a variety of malignant B-cell lines. Tumor cell lysis was Lym-1 specific because (a) the reaction was dose dependent with significant ADCC detectable at Lym-1 concentrations as low as 1 microgram/ml; (b) tumor targets not expressing the Lym-1 antigen were unaffected; (c) an isotype-matched irrelevant monoclonal antibody and an IgG1 anti-Class II monoclonal antibody failed to mediate ADCC; and (d) addition of Protein A (which binds avidly to Lym-1) blocked ADCC by 90 to 100%. Peripheral blood mononuclear cells obtained from normal donors as well as from cancer patients were able to interact with Lym-1 to elicit ADCC. Recombinant interleukin 2 (rIL-2) enhanced non-antibody-mediated tumor lysis and Lym-1 ADCC with an optimal concentration of 100 units/ml. Pulse treatment of normal peripheral blood mononuclear cells with rIL-2 was able to augment Lym-1 ADCC but was less effective than having the rIL-2 present through the assay. Peripheral blood mononuclear cells obtained from patients being treated with high doses of rIL-2 administered by continuous i.v. infusion demonstrated Lym-1 ADCC levels which were higher than normal individuals and which were further augmented by in vitro incubation with rIL-2.

Animals↗
PubMed1989

Antiproliferative mechanism of anti-class II monoclonal antibodies.

The function of Class II molecules in proliferation was explored by treating human cell lines with three distinct anti-DR monoclonal antibodies (MABs). Dose-dependent, specific inhibition of eight DR+ cell lines of different origin and lineage was found. Inhibition was durable (i.e., cells did not become resistant to the anti-DR MABs despite prolonged treatment) yet reversible. The mechanism of inhibition was not due to differentiation or killing but was cytostatic. Inhibition was temporally associated with decreases in nuclear size and irregularity and appeared to be due to a non-phase-specific cell cycle arrest.

Animals↗
PubMed1988

Analysis of human peripheral blood mononuclear cells bearing Fc receptors for the three major immunoglobulin isotypes.

Fluorochrome-labeled, human immunoglobulins (Igs) were used to characterize peripheral blood mononuclear cell (PBMC) subsets that had Fc receptors (FcRs) for the three major isotype classes, IgG, IgA and IgM. Relatively high concentrations of these Igs were needed to saturate FcRs. However, by a number of criteria, competition assays in particular, isotype-specific FcR binding was shown. In vivo bound Ig was directly measured by anti-Fc class-specific F(ab)2 antibodies. With the exception of monocytes, where a mean of 19% had in vivo bound IgG, only small percentages of other PBMC subsets had any type of in vivo bound Ig. Studies done on a large group of normal individuals revealed that approximately 27% of all PBMCs had gamma, 24% alpha, and 23% microFcRs. Dual fluorescence assays were performed to determine the gamma, alpha, and microFcR status on T, B, NK cells and on monocytes. The majority of staining for gamma, alpha, and microFcRs was accounted for by the numerically largest subfraction, the T cells. However, when FcR status was determined for each subset virtually all had either gamma, alpha, or microFcRs--94% of CD2+, 98% of CD4+, 73% of CD8+, 100% of CD19+, 100% of CDw19+, 92% of Leu 7+, and 61% of Leu 11+ cells. All three FcRs were expressed within each subset. Of interest, a small percentage of unfractionated and monocyte-depleted PBMCs coexpressed one of three pairs of FcRs, either alpha and gamma, alpha and mu, or mu and gamma.

Antigens, Differentiation↗
PubMed1985

Antiproliferative monoclonal antibodies: detection and initial characterization.

Two monoclonal antibodies (MAB) are described which inhibit in vitro cellular proliferation in the absence of complement or effector cells. These MAB were produced by hybridomas made from mice immunized against human B lymphoma cells. The MAB were detected by using a colorimetric assay that quantifies proliferation based on the conversion of a yellow tetrazolium salt to a purple formazan product, a reaction that occurs only in metabolically active cells with intact mitochondrial enzymes. A human B lymphoblastoid cell was used as the screening target. RBC4 is an IgM MAB that modulates and immunoprecipitates the transferrin receptor. RBG5 is an IgG1 that binds to a nonmodulating cell surface determinant different from the transferrin receptor. Both MAB are active at low concentrations (RBC4, 0.5 microgram/ml and RBG5, 0.01 microgram/ml). Immunofluorescence staining of cell lines by RBC4 and RBG5 shows little correlation with inhibition by the antibodies. They differentially inhibit the proliferation of a panel of T, B, and myeloid cell lines. Both antibodies inhibit the proliferation of alloantigen or mitogen-activated human peripheral blood lymphocytes (PBL). Unstimulated PBL are not affected by either MAB. The RB MAB each cause different morphologic changes of target cells. Whereas RBC4-inhibited cells exhibit nonspecific changes, RBG5 causes a progressive increase in the size and nuclear number of a subset of inhibited cells.

Animals↗
PubMed1981

Murine autogeneic mixed lymphocyte culture. Role of culture conditions.

In an attempt to determine whether culture conditions significantly influence autoreactivity, we tested the effects of fetal calf, syngeneic, and autogeneic serum with and without 2-mercaptoethanol on the murine self-reactive mixed lymphocyte culture. We used both unfractionated and T-enriched lymph node cells as responders and unfractionated and B-enriched irradiated spleen cells as stimulators in a primary mixed lymphocyte culture (MLC). Using unfractionated cells as responders to various stimulator cell populations, we found excellent allogeneic reactions in all media tested but minimal or no self-reactivity in syngeneic of autogeneic serum. When using T-enriched lymph node cells as responders, allogeneic reactivity was excellent but self-reactivity was present only in the cultures supplemented with fetal calf serum and 2-mercaptoethanol. The possibility that the substances in fetal calf serum and/or 2-mercaptoethanol may be needed to enhance minimal, but biologically relevant, self-reactivity is discussed, as well as the possibility that the culture supplements may be inducing "nonspecific" self-reactivity.

Animals↗
PubMedDate not supplied

Nuclear magnetic resonance spectroscopy of plasma for the detection of head and neck cancer.

The plasma of 15 normal volunteers, four patients with benign head and neck disease, and 12 patients with biopsy proven head and neck malignancies were evaluated using water-suppressed nuclear magnetic resonance (NMR) spectroscopy. While the mean full width at half height (HHLW) of the NMR spectra showed a significant difference between groups (P less than .05), the predictive value of a positive test was only 57% the sensitivity was only 33%, and individual values in all groups demonstrated considerable overlap. The mean HHLW of the control group was 38.5 Hz +/- 3.5 compared with 35.2 Hz +/- 4.7 for the cancer group and 35.0 Hz +/- 10 for the benign disease group. This method was not able to distinguish patients with malignancy from those with benign disease or controls. Its use as a specific screening method for head and neck malignancy cannot be recommended.

Adult↗
PubMedDate not supplied

Recombinant interleukin-6 in the treatment of congenital thrombocytopenia associated with absent radii.

PURPOSE: The role interleukin-6 (IL-6) in the treatment of congenital thrombocytopenias is unknown. The purpose of this case report is to describe the efficacy of IL-6 in a child with thrombocytopenia with absent radii (TAR) syndrome. METHODS: A 23-month-old girl with TAR syndrome was treated with recombinant IL-6 (Sigosix; Serono Laboratories, Norwell, MA) at a dose of 7 micrograms/kg subcutaneously daily. Complete blood counts were monitored weekly. The child was closely monitored for any toxicity. RESULTS: After 3 weeks of therapy, the patient had an increase in platelet count from a baseline of 5,000 to 8,000/microliter to a maximal level of 33,000/microliter. She was platelet transfusion-independent during IL-6 therapy. Fevers and chills, the main toxicities encountered, were controlled with acetaminophen and ibuprofen. An increase in the IL-6 dose caused anemia with no further increase in platelet count. After discontinuation of the drug, her hemoglobin rose to baseline and the platelet count returned to pretreatment levels. CONCLUSIONS: We conclude that IL-6 may benefit some children with TAR syndrome. The role of IL-6 and other thrombopoietic agents in the treatment of TAR and other congenital thrombocytopenias deserves further clinical study.

Administration, Cutaneous↗