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Historical perspectives of allergen immunotherapy
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
David Fitzhugh, Sheldon G. Cohen, Richard Evans
During the late 1930s, allergen vaccines were modified in an effort to decrease the frequency of injections. Depot-like immunogenic materials were prepared to provide a slow, continuous release of allergen from injection sites. The first attempt used ground raw pollen suspended in olive oil [107]. Because particulate bacterial vaccines and modified toxoid proved to be effective immunogens, soluble pollen allergen vaccines were converted to particulate suspensions by alum precipitation and alum adsorption [108,109]. Other modifications included acetylation, heat, and formalin treatment [109]; precipitation by tannic [110] and hydrochloric acids [111]; and a mixture with gelatin [112]. Of these, only alum-adsorbed pollen extracts gained any popularity. Treatment of hay fever with an emulsified allergen vaccine was introduced by Naterman, who in 1937 emulsified a pollen extract with lanolin and olive oil [113]. Thirteen years later, he suspended grass and ragweed pollen tannate in peanut oil with aluminum monostearate [114]. Malkiel and Feinberg, encouraged by evidence of slow absorption from new penicillin-in-oil depot formulations, prepared extracts of ragweed in sesame oil–aluminum monostearate. With these, however, they were unable to avoid constitutional reactions, while failing to reduce the severity of symptoms [115]. Furthermore, other investigators detected increased titers of neutralizing antibody in treated patients without clinical benefit, thus casting doubt on the clinical relevance of “blocking” antibody [116,117].
Opinion: Immunotherapy Has No Place in the Treatment of Recurrent Pregnancy Loss*
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
There have been a number of concepts suggested to explain the mechanism of action of active immunization. None has stood the test of thorough investigation. The first concept of an alloimmune basis for RM was based on an increased sharing of human leukocyte antigens (HLA) between both partners that prevents the maternal production of a “blocking” antibody which protects the fetus against immunological attack [3]. Women with successful pregnancies were thought to produce this “blocking” antibody and those whose pregnancy ends in miscarriage do not. White cell immunization has been reported to induce production of the “blocking” antibody [4]. However, the “blocking antibody” hypothesis has never been validated, and an increased sharing of HLA Class I alleles between partners has been refuted in a number of articles and in Beydoun et al.'s [5] meta-analysis. Further, (a) production of “blocking” antibody is usually not evident until after 28 weeks’ gestation and may disappear between pregnancies [6]; (b) miscarriage occurs despite the presence of “blocking” antibody [7,8], and (c) women who exhibit no production of “blocking” antibodies do experience successful pregnancies. Consequently, the clinical impact of such antibodies is unclear [9]. Leucocyte immunization has also been reported to reduce natural killer cell numbers [10] and modulate cytokine levels in favor of a Th-2 response. These mechanisms have also not been confirmed in large studies, and have not been shown to be relevant to human pregnancies.
Therapeutic Apheresis in Children
Published in James L. MacPherson, Duke O. Kasprisin, Therapeutic Hemapheresis, 2019
A variety of immunotherapies have been tried in neuroblastoma with varying degrees of success. The use of PE in these patients could conceivably reduce the quantity of blocking antibody. A two-year-old patient with metastatic neuroblastoma was treated with PE. The procedure was conducted safely even though the patient weighed only 12 kg. The patient was transfused prior to the exchange and the machine was primed with red cells to minimize the hypovolemic complications. Six PE were conducted and each was associated with mild to moderate hypovolemic problems. Although the results of the therapy was not published, the rationale for PE in this entity makes future attempts likely.32
Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
Published in OncoImmunology, 2023
Tal Flieswasser, Astrid Van den Eynde, Laurie Freire Boullosa, Jöran Melis, Christophe Hermans, Céline Merlin, Ho Wa Lau, Jonas Van Audenaerde, Filip Lardon, Evelien Smits, Patrick Pauwels, Julie Jacobs
LLC-bearing mice were randomized and treated as described above. At day 14, mice were sacrificed and both tumor and TDLN were removed. Tumors were weighed, minced and enzymatically digested with digestion medium (DMEM+10% FBS+10 mm L-glutamine + Collagenase D + DNAse-I) for 60 minutes at 37°C and 5% CO2 in a cell rocker. After digestion, all samples were washed with buffer (PBS+2% BSA+1 mm EDTA) and put through a 70-µm cell strainer to obtain single-cell suspension. Lymph nodes were dissociated mechanically, washed with FACS buffer and put through a 40-µm cell strainer to obtain a single-cell suspension. Single cell suspensions were stained with anti-mouse FoxP3 AF-647 (Clone MF-14), CD103 BV421 (Clone 2E7), CD4 BV570 (Clone RM4–5), NK1.1 BV605 (Clone PK136), CD45.2 BV650 (Clone 104), CD8a BV711 (Clone 53–6.7), CD11c BV785 (Clone N418), CD25 PE (Clone 3C7), CD3 PE/Fire 700 (Clone 17A2, all purchased from Biolegend) and Live/Dead Fixable Near IR APC-Cy7 (ThermoFisher). Prior to antibody staining, all cell suspensions were treated with Fc blocking antibody (1:100, Clone 2.4G2, BD Biosciences) to avoid aspecific binding of antibodies. The cell numbers in tumors were corrected for differences in tumor weight (Number of cells/Tumor weight). Fold changes were compared to the untreated control (vehicle) group. Intraperitoneal tumors were excluded from further analysis. All samples were analyzed using a Novocyte Quanteon flow cytometer.
Presence of macroproteins on the measurement of vitamin B12: studying high vitamin B12 levels using polyethylene glycol and heterophile antibody blocking tubes
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2023
Heterophilic antibodies bind to animal antibodies used in immune measurements and cause interference in these tests. It has been reported that they generally cause falsely high results and sometimes false low results [18]. Although heterophile antibody interference is a rare condition; the geographic region in which individuals live is closely related to exposure to animals or animal products. Although they are present in 30-40% of serum samples, the probability of causing interference is 0.05% [36]. Heterophilic antibody interference can occur in all types of immune measurement methods, but it mostly affects noncompetitive immune measurements [18,37,38]. In the measurement of vitamin B12 with the competitive immune method used in this study, there was a denaturing stage with polyclonal antibodies aimed at reducing heterophile antibody interference. In addition, commercially available HBTs do not guarantee 100% success, and the absence of a meaningful result does not mean that there is no interference. The antibodies found in our patients may not have been recognized by the blocking antibody in HBT, or the presence of antibodies in very high titers may also eliminate the blocking feature of the tubes [39].
Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
Published in OncoImmunology, 2021
Mark A.J.M. Hendriks, Isabel Britsch, Xiurong Ke, Anne P. van Wijngarden, Douwe F. Samplonius, Emily M. Ploeg, Wijnand Helfrich
The following unconjugated antibodies directed against human antigens were used: anti-SIRPγ antibody (clone LSB2.20, Santa Cruz Biotechnology), anti-CD47 antibody (B6H12, ThermoFisher), antagonistic anti-TRAIL antibody (clone 2E5, Abcam), antagonistic anti-FASL antibody (clone 2 C101, Enzo Life Sciences), agonistic anti-FAS antibody (clone 7C11, Immunotech), antagonistic anti-IFNγ antibody (clone B27, Immunotools), antagonistic anti-TNFα antibody (clone D2E7, Enzo Life Sciences), EGFR-blocking antibody (clone 425, Merck). SIRPα-Fc (TTI-621, Trillium Therapeutics) and anti-human CD47-IgG4 antibody (CC-90002, Inhibrix) were generated by commercial gene synthesis service (GenScript). Fluorescently labeled secondary antibody goat anti-human Ig PE and goat anti-mouse IgG APC were both from Southern Biotech.