preclinical evaluation and clinical application of novel cross-modal, multidisciplinary...
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Preclinical Evaluation and Clinical Application of
Novel Cross-Modal, Multidisciplinary Bio-
Technology with Anti-Radiation Prophylaxis (Anti-
Radiation Vaccine) and Therapy Regimens (Anti-
Radiation Antidote) and Anti-Cancer Post-Radiation Prophylaxis.
DMITRI POPOV. PHD, RADIOBIOLOGY.
MD (RUSSIA)
ADVANCED MEDICAL TECHNOLOGY AND SYSTEMS INC. CANADA.
Anti-radiation vaccine, Anti-
radiation Antidote.
DOI: 10.13140/RG.2.1.2014.0244
Anti-radiation vaccine, Anti-
radiation Antidote.
Anti-Radiation protection technology include Anti-radiation
Vaccine and Anti-radiation Antidote consisting of novel biologicals
and targeted proteolytic, hydrolytic enzymes and their key pathways for activation in post-radiation apoptosis, post-radiation
necrosis, inflammation, autoimmunity, cytotoxicity, radiation
vasculitis, DNA damage, and post-radiation neoplasms were tested
alone, and in combination with radiation, placebo, monoclonal
antibodies, inhibitors of proteases, agonists and antagonists for
receptors of T lymphocytes and B lymphocytes.
Anti-radiation vaccine, Anti-
radiation antidote.
Our investigation include immune inhibition and neutralisation of
post-radiation cytotoxicity.
Our investigation include development anti-radiation vaccine, anti-radiation antidote.
Anti-radiation vaccine, Anti-
radiation Antidote.
Project 1. Anti-radiation Vaccine.
Anti-radiation Vaccine: pre-radiation vaccination with T – Lymphocytes and B-Lymphocytes, isolated from blood or lymph of mammal irradiated with high doses of gamma radiation.
Anti-radiation Vaccine: pre-radiation vaccination with hydrolytic enzymes isolated from lysosomes of neutrophils, isolated from blood or lymph of mammals, irradiated with high doses of gamma radiation.
Anti-radiation Vaccine: pre-radiation vaccination with molecular structures which mimicking the receptors of T-Lymphocytes (radiation activated and rearranged) and B-Lymphocytes (radiation activated and re-arranged, isolated from lymph or blood of irradiated with high doses of irradiated mammals.
Anti-radiation vaccine, Anti-
radiation antidote.
Explanation.
“The B-cell receptor or BCR is a transmembrane receptor
protein located on the outer surface of B-cells. The receptor's
binding moiety is composed of a membrane-bound antibody that,
like all antibodies, has a unique and randomly determined antigen-
binding site. When a B-cell is activated by its first encounter with an
antigen that binds to its receptor (its "cognate antigen"), the cell
proliferates and differentiates to generate a population of antibody-
secreting plasma B cells and memory B cells. ”
Anti-radiation vaccine, Anti-
radiation antidote.
“The B cell receptor (BCR) has two crucial functions upon interaction
with the antigen.
One function is signal transduction, involving changes in receptor oligomerization.
The second function is to mediate internalization for subsequent
processing of the antigen and presentation of peptides to helper T
cells.
BCR functions are required for normal antibody production, and
defects in BCR signal transduction may lead to immune-
deficiency, auto-immunity and B-cell malignancy.”
Anti-radiation vaccine, Anti-
radiation antidote.
“The T cell receptor or TCR is a molecule found on the surface of T
lymphocytes (or T cells) that is responsible for recognizing
antigens bound to major histocompatibility complex (MHC) molecules.
The binding between TCR and antigen is of relatively low affinity and
is degenerate: that is, many TCRs recognize the same antigen and
many antigens are recognized by the same TCR.”
Anti-radiation vaccine, Anti-
radiation antidote.
“T helper cells: The T helper cells (Th cells) are a type of T cell that
play an important role in the immune system, particularly in
the adaptive immune system.
They help the activity of other immune cells by releasing T
cell cytokines.
These cells help suppress or regulate immune responses. They are
essential in B cell antibody class switching, in the activation and
growth of cytotoxic T cells, and in maximizing bactericidal activity
of phagocytes such as macrophages. ”
Anti-radiation vaccine, Anti-
radiation antidote.
“Mature Th cells express the surface protein CD4 and are referred to
as CD4+ T cells.
Such CD4+ T cells are generally treated as having a pre-defined role as helper T cells within the immune system.
For example, when an antigen-presenting cell expresses an antigen
on MHC class II, a CD4+ cell will aid those cells through a
combination of cell to cell interactions (e.g. CD40 and CD40L) and
through cytokines.”
Anti-radiation vaccine, Anti-
radiation antidote.
“T killer cells: A cytotoxic T cell (also known as TC, cytotoxic T
lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cells or killer T
cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or
cells that are damaged in other ways.”
Anti-radiation vaccine, Anti-
radiation antidote.
“Most cytotoxic T cells express T-cell receptors (TCRs) that can
recognize a specific antigen.
An antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses.
Antigens inside a cell are bound to class I MHC molecules, and
brought to the surface of the cell by the class I MHC molecule,
where they can be recognized by the T cell.
If the TCR is specific for that antigen, it binds to the complex of the
class I MHC molecule and the antigen, and the T cell destroys the
cell.”
Anti-radiation vaccine, Anti-
radiation antidote.
T and B cells, which specifically activated after irradiation, induce
cell necrosis, inflammation, and autoimmune, immune-toxic and cytotoxic reactions.
Rearranged receptors of T and B cells – under influence of radiation
– recognize changed antigenic specificity of irradiated tissues as
foreign, activate immune cytotoxic reaction.
Anti-radiation vaccine, Anti-
radiation antidote.
Project 2. Anti-Radiation Antidote.
Anti-Radiation Antidote: post-radiation therapy with monoclonal antibodies to rearranged receptors of T – Lymphocytes and B-Lymphocytes, isolated from blood or lymph of mammal irradiated
with high doses of gamma radiation.
Anti-radiation vaccine, Anti-
radiation antidote.
Blocking monoclonal antibodies to rearranged receptors of T-
Lymphocytes and B-Lymphocytes, isolated from blood or lymph of
irradiated mammals, prevent radiation toxicity, cell necrosis, cell and cytotoxicity, prevent and protect cell structures and cell
membranes, prevent leakage of hydrolytic enzymes from lysosomes,
prevent radiation induced vasculitis, neurotoxicity, induced
hematopoietic marrow protection, prevent DNA damage.
Anti-radiation vaccine, Anti-
radiation antidote.
Anti-Radiation Antidote include monoclonal antibody to some
important hydrolytic enzymes.
Anti-radiation vaccine, Anti-
radiation antidote.
Anti-Radiation Antidote include monoclonal antibody to groups of
Histamine receptors.
The histamine receptors are a class of G protein–coupled receptors with histamine as their endogenous ligand.
Anti-radiation vaccine, Anti-
radiation antidote.
The H1 receptor is a histamine receptor belonging to the family
of Rhodopsin-like G-protein-coupled receptors. This receptor, which
is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on
vascular endothelial cells, in the heart, and in the central nervous
system. The H1 receptor is linked to an intracellular G-protein (Gq)
that activates phospholipase C and the phosphatidylinositol (PIP2)
signaling pathway.
Anti-radiation Antidote include monoclonal antibody to H1
receptor.
Therapy of Cerebrovascular, Cardiovascular Radiation Syndromes,
Post-radiation vasculitis.
Anti-radiation vaccine, Anti-
radiation antidote.
“H2 receptors are positively coupled to adenylate cyclase via Gs. It is
a potent stimulant of cAMP production, which leads to activation
of Protein Kinase A.
PKA functions to phosphorylate certain proteins, affecting their
activity. The drug betazoleis an example of a Histamine H2 receptor
agonist.
Anti-radiation vaccine, Anti-
radiation antidote.
Histamine is a ubiquitous messenger molecule released from mast
cells, enterochromaffin-like cells, and neurons.[1] Its various actions
are mediated by histamine receptors H1, H2, H3 and H4. The histamine receptor H2 belongs to therhodopsin-like family of G
protein-coupled receptors.
It is an integral membrane protein and stimulates gastric acid
secretion. It also regulates gastrointestinal motility and intestinal
secretion and is thought to be involved in regulating cell growth
and differentiation”.
Monoclonal antibody against H2 - therapy of Gastrointestinal Acute Radiation Syndrome.
Anti-radiation vaccine, Anti-
radiation antidote.
Activation of the H2 receptor results in the following physiological responses:
Stimulation of gastric acid secretion (Target of anti-histaminergics (H2 receptors) for peptic ulcer disease and GERD)
Smooth muscle relaxation (Experimental histamine H2 receptor agonist used for asthma and COPD)
Inhibit antibody synthesis, T-cell proliferation and cytokine production
Vasodilation – PKA activity causes phosphorylation of MLCK, decreasing its activity, resulting in MLC of myosin being dephosphorylated by MLCP and thus inhibiting contraction. The smooth muscle relaxation leads to vasodilation.
Monoclonal antibody to H2 histamine receptors.
Anti-radiation vaccine, Anti-
radiation antidote.
Histamine H3 receptors are expressed in the central nervous system and to a lesser extent the peripheral nervous system, where they act as autoreceptors in presynaptic histaminergic neurons, and also control histamine turnover by feedback inhibition of histamine synthesis and release. The H3 receptor has also been shown to presynaptically inhibit the release of a number of other neurotransmitters (i.e. it acts as an inhibitory heteroreceptor) including, but probably not limited to dopamine, GABA, acetylcholine, noradrenaline, histamine andserotonin.
The gene sequence for H3 receptors expresses only about 22% and 20% homology with both H1 and H2 receptors respectively.
Monoclonal Antibody to H3.
Anti-radiation vaccine, Anti-
radiation antidote.
The histamine H4 receptor is, like the other three histamine receptors,
a member of the G protein-coupled receptor superfamily.
H4 is highly expressed in bone marrow and white blood cells and regulates neutrophil release from bone marrow and subsequent
infiltration in the zymosan-induced pleurisy mouse model.[4] It is also
expressed in the colon, liver, lung, small intestine, spleen, testes,
thymus, tonsils, and trachea.
Monoclonal antibody to H4 receptors.
The Histamine H4 receptor has been shown to be involved in
mediating eosinophil shape change and mast cell chemotaxis.[ This occurs via the βγ subunit acting at phospholipase C to cause actin
polymerisation and eventually chemotaxis.
Anti-radiation vaccine, Anti-
radiation antidote.