PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11544832

[A novel immunoregulating hexapeptide with antineoplastic effect].

E M Treshchalina·L A Sedakova·N K Vlasenkova·O S Zhukova·G A Firsova·L M Mikhaĭlova·E Iu Kolesnikova·N I Zimakova·S V Khabarov·G K Gerasimova
View original source ↗Export metadata ↓

Abstract

A synthesized analog of myelopeptide HP-2-->M[symbol: see text]-2 (Leu-Val-Val-Tyr-Pro-Trp) caused a significant (60-80%) and prolonged inhibition of s.c. grafted tumors P388, Ca-755, B-16 and sarcoma 180 in isogenic mice but did not affect the growth of tumor B-16 in nude mice. Nor did it influence proliferative activity or viability of cultured human tumor cells. The best results were obtained with s.c. injections of 0.5-2 mg/kg HP-2-->M[symbol: see text]-2, twice or trice a day, at 96 hr intervals. No symptoms of severe poisoning were registered at doses of HP-2-->M[symbol: see text]-2 100 times the therapeutic one. A pharmacokinetic study in mice revealed prolonged circulation of HP-2-->M[symbol: see text]-2 in blood and a high affinity for the bone marrow (t 1/2 (130.1 hr and 431.6 hr, respectively). HP-2-->M[symbol: see text]-2 restored in vitro the ascites P388-suppressed cytotoxicity of murine T-lymphocytes. HP-2-->M[symbol: see text]-2 is regarded as a candidate for clinical studies of its potential of immunocorrection in cancer patients suffering T-lymphocyte immunity disturbances.

Explore related subjects

Adjuvants, ImmunologicAnimalsAntineoplastic AgentsCell DivisionFemaleHumansImmunologic FactorsLeukemia P388MaleMammary Neoplasms, ExperimentalMelanoma, ExperimentalMiceMice, Inbred BALB CMice, Inbred DBANeoplasms, ExperimentalOligopeptidesSarcoma 180T-LymphocytesTumor Cells, CulturedEnglish AbstractJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E M Treshchalina, L A Sedakova, N K Vlasenkova, O S Zhukova, G A Firsova, L M Mikhaĭlova, E Iu Kolesnikova, N I Zimakova, S V Khabarov, G K Gerasimova. 2001. [A novel immunoregulating hexapeptide with antineoplastic effect].. https://pubmed.ncbi.nlm.nih.gov/11544832/

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↗