PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 2819484

Multistep scheme for testing immunomodulatory substances.

A Macela·H Kovárová·J Stulík·M Ferencík·P Propper·E Hosková
View original source ↗Export metadata ↓

Abstract

The presented multistep program for testing immunomodulatory properties of biological response modifiers offers the possibility to evaluate multilaterally the modulatory potential of the tested preparations and to obtain basic data concerning their acute immunotoxicity. The scheme is divided into four stages: screening, optimalization, modelling, and analytical stage, each of which can be carried out separately on a relatively individual basis. This division considers the effect of the preparation on basic functions of the cells participating in the network of immunoregulation, the influence on the course of the immune response, modulation of the reactivity of the immune system affected by a 'non-immunological' phenomenon, as well as changes in protein repertoire produced by different systems of cells exposed to the tested preparation and/or the immunogenic signal. Detailed toxicological evaluation should be performed separately from immunopharmacological evaluation, keeping in mind differences in the application of the substances and the animal model involved. Incorporation of mathematical modelling and computer analysis of the results obtained by using the scheme may prove valuable in solving problems associated with potential modulation of the host immune system in clinically significant situations.

Explore related subjects

Adjuvants, ImmunologicAnimalsDrug EvaluationDrug Evaluation, PreclinicalHumansImmunityJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Macela, H Kovárová, J Stulík, M Ferencík, P Propper, E Hosková. 1989. Multistep scheme for testing immunomodulatory substances.. https://pubmed.ncbi.nlm.nih.gov/2819484/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response.

Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA [isRNA]) are potent inducers of interferon-alpha via the Toll-like receptor 7. We investigated the effect of isRNA on the development of an immune response. We show that isRNA activates dendritic cells and induces production of Th1-type cytokines both in vitro and in vivo. Cytokine production led to bystander activation of T and B cells. We further demonstrate that isRNA triggers the generation of antigen-specific cytotoxic T cells and of an IgG2a-biased antibody response to antigen in a sequence-dependent manner. In summary, we provide evidence for the first time that isRNA oligonucleotides can simultaneously activate the innate and adaptive arms of the immune system.

Adjuvants, Immunologic↗
PubMed2007

Mechanism of third signals provided by IL-12 and OX-40R ligation in eliciting therapeutic immunity following dendritic-tumor fusion vaccination.

Dendritic-tumor heterokaryons generated by electrofusion are highly immunogenic. In animal studies, a single vaccination was therapeutic for tumors established in the lung, skin, and brain. However, effective therapy required a third signal which could be provided by exogenous IL-12 or the agonistic anti-OX-40R monoclonal antibody (mAb). In this study, we investigated the mechanism and mode of actions of these two seemingly distinct adjuvants. In immunotherapy of the MCA205 sarcoma, administration of the neutralizing anti-IL-12 mAb nearly completely blocked the adjuvant effect of IL-12, but had minimal inhibitory effects on anti-OX-40R mAb. By contrast, in vivo administration of the antagonistic anti-OX-40L mAb inhibited the adjuvant effects of both IL-12 and anti-OX-40R mAb. Thus, a common pathway of endogenous OX-40 interaction is critical for the development of a therapeutic immune response. Analysis of the third signal mechanism revealed that in the absence of an adjuvant, vaccination with fusion hybrids led to IL-10 production without eliciting IFN-gamma secreting cells. The addition of IL-12 to vaccination suppressed IL-10 production and initiated sensitization of specific IFN-gamma secreting cells, resulting in a type 1-like antitumor immunity. These findings underscore the significance of the third signal in the design of dendritic cell-based cancer vaccines.

Adjuvants, Immunologic↗