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Soluble Tumor Antigens Used in Clinical Trials of Immunotherapy
Published in Thomas H. M. Stewart, E. Frederick Wheelock, Cellular Immune Mechanisms and Tumor Dormancy, 2017
Additional experiments using Freund's complete adjuvant (FCA) were carried out10. Three groups of 24 hamsters were injected with 104, 105, and 106 tumor cells, respectively. Half of the animals in each group were given FC A intraperitoneally 17 days before subcutaneous adenovirus-induced tumor cell challenge; the other half were not pretreated. All animals injected with FCA developed tumors, whereas in the hamsters receiving no adjuvant, one-third of those inoculated with 104 cells, one-half of those inoculated with 105 cells, and all of those inoculated with 106 cells developed tumors. Thus, these findings illustrated that general stimulation of the lymphoreticular system by nonspecific materials might produce deleterious results. The effect of this stimulation greatly depends upon the type and site of tumor and the type of immune response predominant in the host at the time of injection with nonspecific adjuvant. For example, BCG cell-wall skeleton oil-water, BCG or FCA might stimulate the existing host response we reported as present in early stage melanoma, whereas the use of these nonspecific adjuvants in the late stage of the disease might cause havoc since we find that the majority of these patients react to the wrong antigens11. In our studies, we reported12 that the opposite occurs in many breast cancer patients, and the use of nonspecific active immunotherapy in early stage breast cancer seems inappropriate.
Clinical applications of hyperthermia in cancer treatments
Published in Clifford L. K. Pang, Kaiman Lee, Hyperthermia in Oncology, 2015
Clifford L. K. Pang, Kaiman Lee
It adopts intraperitoneal perfusion of interleukin-2, Streptococcus A group for injection, tumor necrosis factor and nocadia rubra cell wall skeleton, interferon-α; and Corynebacterium parvum, which have produced sound effects on most therapies of cancerous ascites.
Novel insights into the pharmacometabonomics of first-line tuberculosis drugs relating to metabolism, mechanism of action and drug-resistance
Published in Drug Metabolism Reviews, 2018
EMB invades the M. tuberculosis cells via porin channels and subsequently inhibits cell wall synthesis by interacting with the EmbCAB enzymes. The embCAB operon encodes a series of arabinofuranosyltransferases, which are involved in arabinofuranosyl (Araf) polymerization from DPA β-d--arabinofuronosyl-1-monophosphoryl decaprenol), in order to synthesize arabinogalactan (AG) and lipoarabinomannan (LAM) (Figure 4) (Arbex et al. 2010; Sahu et al. 2015). The EmbA and EmbB enzymes transfer Araf residues to a galactan chain after the initial Araf residues are linked to galactan by another priming arabinofuranosyltransferase, AftA (encoded by Rv3792). EmbC also uses DPA as the donor to transfer Araf residues to a mannan core after the Araf residues are linked to mannan by an uncharacterized arabinofuranosyltransferase (Safi et al. 2013). EMB-induced inhibition of EmbCAB, and the consequent disruption of AG and LAM syntheses, ultimately disturbs the synthesis of the M. tuberculosis cell wall skeleton, which comprises of a mycolyl-arabinogalactan-peptidoglycan complex, and the important cell wall glycoconjugate, LAM, thereby interfering with normal bacterial growth, and eventually causing bacterial cell death (Sahu et al. 2015).
A review of recent developments on micro/nanostructured pharmaceutical systems for intravesical therapy of the bladder cancer
Published in Pharmaceutical Development and Technology, 2018
Marcela Brito Oliveira, Mônica Villa Nova, Marcos Luciano Bruschi
Nakamura and collaborators developed a system for intravesical delivery of the BCG-cell wall skeleton (CWS) to treat superficial BC. The BCG-CWS is the key factor to the immunological response, which acts like a replenishing to the live BCG. The authors used egg phosphatidylcholine (PC), cholesterol and stearylated octa-arginine to form the lipid film, which was further extruded through a 400 nm membrane to form the liposomes. The BCG-CWS was incorporated into the liposomes using a sonicator probe and an emulsification/solvent evaporation technique, followed by a new extrusion of the material. Despite the unfavorable physical properties of the pure drug, such as low water solubility, high molecular weight, heterogeneity of particle size, formation of aggregates and low efficacy the resultant liposomal complex decreased aggregation of the drug, reduced tumor size showing an anti-proliferative action and increased internalization by neoplastic cells (Nakamura et al. 2014).
Mycobacterium bovis BCG-mediated suppression of Th17 response in mouse experimental autoimmune encephalomyelitis
Published in Immunopharmacology and Immunotoxicology, 2021
Goro Matsuzaki, Naoko Teruya, Hideyasu Kiyohara Kohama, Keiko Arai, Yukihiro Shibuya, Yasushi Chuma, Kazuhiro Matsuo
The objective of the study therefore is to establish an EAE system induced without Mtb in adjuvant and clarify the influence of BCG inoculation on EAE development using this system. Cell wall skeleton (CWS) is a protein antigen-deprived cell wall extract of BCG [16] with strong stimulant activity to innate immunity [17]. We established an EAE model induced by immunization of C57BL/6 mice with MOG35-55 peptide emulsified in incomplete Freund’s adjuvant (IFA) with CWS as an adjuvant (CWS-EAE). BCG inoculation into the CWS-EAE mice 6 d after the induction resulted in ameliorated clinical symptoms and reduced counts of Th17 cells in the CNS. The implications of the observations are discussed.