IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients

Franco‐Molina, Moises Armides; Mendoza‐Gamboa, Edgar; Zapata‐Benavides, Pablo; Vera-García, M.E.; Castillo-Tello, Paloma; Fuente, A. García de la; Mendoza, Roseann; Garza, Rocío García de la; Taméz-Guerra, Reyes; Rodríguez‐Padilla, Cristina

doi:10.1080/14653240802165681

Cited by 33 publications

(31 citation statements)

References 28 publications

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“…DLE has demonstrated to be effective in those diseases in which Cell-Mediated Immunity (CMI) plays a relevant role in protection against and control of the disease, such as viral infections ((herpes zoster [17], hepatitis B [18], intracellular bacterial diseases like tuberculosis [19] and leprosy [20], parasite infections, such as leishmaniasis [21] or cryptosporidiosis [22], and fungal infections (mucous-cutaneous candidiasis [23]), as well as in primary immunodeficiencies (Wiskott Aldrich syndrome [24], Behçet's syndrome [25]), bronchial asthma [26], otitis media [27], uveitis [28]) and some types of cancer [29,30]. …”

Section: Introductionmentioning

confidence: 99%

“…Previously we reported that bovine DLE (bDLE) was useful as an adjuvant in breast cancer patients undergoing chemotherapy, demonstrating protective effects against myelosuppression secondary to antitumoral drugs by improving cellular and humoral immunity, as well as in regulating the production of different cytokines involved in cellular proliferation [16,29,30]. Furthermore, in vitro assays demonstrated that bDLE affected the regulation of the expression of p53, bab-1, c-myc, bax, bcl-2 and bad mRNA [31,32].…”

Section: Introductionmentioning

confidence: 99%

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Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

et al. 2011

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BackgroundBovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays.ResultsThe cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action.HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-β-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours.ConclusionsbDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours.bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

et al. 2011

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“…ICRP exhibits in vitro cytotoxic effects on different tumor cell lines and modulates the immune response in vivo (35–40). The aim of the present study was to determine whether ICRP or ICRP combined with OXP induced ICD and prevented melanoma growth.…”

Section: Introductionmentioning

confidence: 99%

The novel immunomodulator IMMUNEPOTENT CRP combined with chemotherapy agent increased the rate of immunogenic cell death and prevented melanoma growth

et al. 2017

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Immunogenic cell death is a cell death modality that stimulates the immune system to combat cancer cells. IMMUNEPOTENT CRP (ICRP) is a mixture of substances of low molecular weight obtained from bovine spleens that exhibits in vitro cytotoxic activity on different tumor cell lines and modulates the immune response in vivo. The aim of the present study was to determine whether the cytotoxic effect of ICRP and its combination with oxaliplatin (OXP) on murine melanoma B16F10 cells was due to immunogenic cell death. The cytotoxic assay was performed using flow cytometry to detect Annexin V and propidium iodide staining, and calreticulin (CRT) exposure. Adenosine triphosphate, heat shock protein (HSP) 70, HSP90 and high mobility group box 1 (HMGB1) release were identified using bioluminescence, western blot and ELISA assays, respectively. The present in vitro study demonstrated that treatments with ICRP or OXP induced cell death in a time-dependent manner, but treatment with the combination of ICRP + OXP increased the cytotoxic effect following 24 h of treatment. CRT exposure and release of adenosine triphosphate (ATP), HSP70, HSP90 and HMGB1 were induced by treatment with ICRP, and the combination of ICRP + OXP increased the exposure and release of damage-associated molecular patterns (DAMPs), while OXP treatment only induced CRT exposure, ATP and HMGB1 release. The in vivo experiments demonstrated that administration of tumor-derived DAMP-rich cell lysates derived from B16F10 cells treated with ICRP and the combination of ICRP + OXP prevented melanoma growth; however, OXP treatment did not. These results suggested that IMMUNEPOTENT CRP may be used as an agent to increase the ability of antitumor drugs to induce immunogenic cell death and prevent the growth of melanoma.

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“…Continuing their previous research, Franco-Molina et al [47] showed that adjuvant immunotherapy with bovine dialyzable leukocyte extract (in the form of the preparation IMMUNEPOTENT CRP) against lung cancer can cause an immunomodulatory effect. Twentyfour NSCLC patients were included in the study and divided into two groups.…”

Section: Cancermentioning

confidence: 99%

Immunotherapy with Dialyzable Leukocyte Extracts Containing Transfer Factor

Arnaudov¹

2017

Immunotherapy - Myths, Reality, Ideas, Future

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Dialyzable leukocyte extracts (DLE) are complexes consisting of a large number of low molecular weight substances. These extracts possess immunomodulatory properties, which are mainly attributed to small peptides with molecular weight of 3.5-6.0 kDa called "transfer factor." This chapter reviews the nature and immunological characteristics of DLE containing transfer factor (TF), their mechanism of action and the possible uses as immunomodulators in human and veterinary medicine. A main advantage of TF-preparations as immunotherapeutic agents is that they induce a rapid immune response against the pathogen (within 24 h) and thereby reduce the time for the patient immune response by 9-13 days. The low level of difficulty of the process of obtaining protocols determines their relatively low cost and the possibility to combine them with other therapeutic agents during treatment makes them subject to medical applications in the future, including against some new diseases.

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IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients

Cited by 33 publications

References 28 publications

Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

The novel immunomodulator IMMUNEPOTENT CRP combined with chemotherapy agent increased the rate of immunogenic cell death and prevented melanoma growth

Immunotherapy with Dialyzable Leukocyte Extracts Containing Transfer Factor

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