Interstitial transfer factor as adjuvant immunotherapy for experimental glioma

Neuroimmunology Unit, National Institute of Neurology and Neurosurgery of Mexico, Mexico City.
Journal of experimental & clinical cancer research: CR (Impact Factor: 3.27). 12/2005; 24(4):575-83.
Source: PubMed

ABSTRACT Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells which transmit the ability to express delayed-type hypersensitivity and cell mediated immunity from sensitized donors to nonimmnune recipients. In this study, we determined the efficacy of TF as immunotherapy to treat experimental glioblastoma. We used TF obtained from immunized swine. We evaluated different doses of intratumoral TF (product of 4x10(6), 8x10(5) and 1.6x10(5) cells). The best dose (product of 4x10(6) cells) of TF was also combined with carmustine for experimental therapy in rats with C6 malignant glioma. Modifications in peripheral blood T lymphocyte counts ( CD2+, CD4+, CD8+ and NK) were evaluated by flow cytometry. Cytokine expression in the tumour was assessed by RT-PCR and apoptosis was evaluated using the sub G0 method. Intratumoral TF reduced significantly the tumour size, and increased CD2+, CD4+, CD8+ and NK cell counts, it also increased the percentage of apoptotic tumour cells and the percentage of tumour tissue expressing Th1 cytokines. We observed an additive antitumoral effect when TF was combined with chemotherapy.

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    • "Immunomodulation by Transferon® has been demon‐ strated by restoration of iNOS expression in a mouse model of tuberculosis, provoking inhibition of bacterial proliferation and significant increase of DTH [17] Transferon® also in‐ duces mRNA expression and IFN-γ secretion in peripheral blood mononuclear cells (PBMC) in animals with experimental glioma when compared with non-treated animals. [18] Due to Transferon® induces a Th1 response a clinical study comparing acyclovir treatment and Transferon® during human herpes virus infection was conducted; in that study patients treated with Transferon® had low incidence of clinical complications, better pain control, and also IFN-g was significant increased in serum when compared with patients treated on‐ ly with acyclovir. [19] Then, our group conducted a second clinical trial to evaluate immu‐ nological data and clinical outcome of patients with HSK treated with acyclovir or acyclovir and Transferon® as adjuvant therapy in patients with herpetic keratitis. "
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    ABSTRACT: The ocular surface is a functional unit mainly formed by the conjunctival and corneal epithelium (structural component), and tear film (soluble component). Microorganisms and environmental allergens can interact with the tear film, reach the structural component and generate an immune response against them. Understanding the cellular and soluble mediators that are involved in these inflammatory responses not only helps in understanding the mechanisms of current treatments, but also is needed to identification and development of new therapeutics targets. The aim of this review was to investigate the novel and developing therapies, with special emphasis in immunomodulatory drugs/molecules that could have some clinical indication in the treatment of infectious and allergic conjunctivitis in few years.
    Common Eye Infections, Edited by Imtiaz A. Chaudhry, 05/2013: chapter Treatments in Infectious and Allergic Conjunctivitis: Is Immunomodulation the Future?: pages 45-60; InTech., ISBN: 978-953-51-0926-6
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    • "Similar results were recorded in murine tuberculosis treated with TF and antibiotics (Fabre et al. 2004). Th1-inducing effect of TF was also confirmed in anti-tumour immunotherapy (Pineda et al. 2005). The serum concentration of IL-5 in mice infected with E. multilocularis and treated with TF or combination of TF +ABZ in our study was inhibited till the end of the experiment. "
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    ABSTRACT: The effect of dialysable leucocyte extract (transfer factor TF) on immune response of mice infected with Echinococcus multilocularis and treated with albendazole (ABZ) was observed. TF administration increased the parasite-suppressed proliferative response of T and B lymphocytes of infected mice from weeks 8 to 12 or 14 post infection (p.i.), respectively, with the most stimulative effect after TF+ABZ therapy. The CD4 T cell presence in the spleen of infected mice with TF or TF+ABZ therapy was increased from weeks 6 to 12 or 14 p.i., respectively. The production of IFN-gamma (Th1 cytokine) after TF or TF+ABZ therapy was significantly higher from weeks 6 to 12 p.i., and during this time, the significantly inhibited IL-5 synthesis (Th2 cytokine) was detected, particularly after TF+ABZ therapy. The superoxide anion (O2-) production in peritoneal macrophages of infected mice treated with TF or TF+ABZ was stimulated from weeks 8 to 18 p.i. The immunomodulative effect of TF reduced the growth of larval cysts till week 14 p.i. with a comparable intensity to the anthelmintic drug ABZ. Combined therapy TF+ABZ resulted in the greatest parasite restriction and reduced the cyst development till the end of the experiment.
    Parasitology Research 07/2009; 105(4):1067-76. DOI:10.1007/s00436-009-1520-z · 2.33 Impact Factor
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    ABSTRACT: Protection of cells against HIV infection by the Dialyzable Leukocyte Extract prior to cell culture duplication. The search for new therapeutic agents to treat the acquired immunodeficiency syndrome (AIDS) continues, since therapeutic anti-retroviral combinations already employed to treat AIDS patients do not eradicate the human immunodeficiency virus (HIV) infection. Our group recently demonstrated the inhibitory effect of the Dialyzable Leukocyte Extract (DLE) on HIV replication in cells, by using an in vitro assay system in the human MT4 cell line. We have also reported a long-term inhibition of viral replication when cells were treated with this leukocyte derivative, prior to viral challenge. In the present trial, our results showed that the DLE-mediated inhibition of HIV in cultured MT4 cells did not depends on cellular duplication, and its inhibitory effect on viral replication is achieved by cellular exposure to DLE for at least 24 h. Inhibition is absent when cells are incubated for shorter periods of time, suggesting that the inhibitory mechanism triggered by DLE is more strongly related to the modification of cellular factors than to its direct action on the viral particle. Modification of viral factors during the virus replication cycle is also considered.
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