Glycoprotein 100, gp100 or Melanocyte protein PMEL is 661 amino acids long and is a type I transmembrane glycoprotein enriched in melanosomes, which are the melanin-producing organelles in melanocytes. This protein is involved in melanosome maturation.
The gp100 protein is a melanoma antigen i.e. a tumor-associated antigen.
Short fragments of it have been used to develop the gp100 cancer vaccine which is or contains gp100:209-217(210M). [1]
Hydrophilic recombinant gp100 protein (HR-gp100) has been topically applied on human intact skin in vitro, and used as a vaccine in a mouse model. It was demonstrated that HR-gp100 permeates into human skin, and is processed and presented by human dendritic cells. In the mouse model, an HR-gp100-based vaccine triggered antigen-specific T cell responses, as shown by proliferation assays, ELISA and intracellular staining for IFN-γ.
Glycoprotein 100 (GP100) is a 661 amino acid long protein that contains differentiation antigens. GP100 is a membrane bound protein that is expressed in melanocytes and pigmented cells in the retina, and in most malignant melanomas. It has widely studied to be used as a target for melanoma immunotherapy. GP100 works in functions melanogensis, melanosome biogenesis, and melanin polymerization (Eisenberg)
There are different sequences of the GP100 peptide that could be used for immunization against tumors. According to a case study, modifications of GP100 such as GP100-209 and GP100-208 have shown a greater number of antigen specific CTL's (cytotoxic T lymphocytes) which can target and kill cancer cells (Eisenberg).
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer of the skin's epidermis, the middle layer of the eye, the inner ear, vaginal epithelium, meninges, bones, and heart. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system.
Glycoproteins are proteins which contain oligosaccharide chains (glycans) covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.
A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation. It is found inside melanosomes which are synthesized in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR gene.
Thy-1 or CD90 is a 25–37 kDa heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored conserved cell surface protein with a single V-like immunoglobulin domain, originally discovered as a thymocyte antigen. Thy-1 can be used as a marker for a variety of stem cells and for the axonal processes of mature neurons. Structural study of Thy-1 led to the foundation of the Immunoglobulin superfamily, of which it is the smallest member, and led to some of the initial biochemical description and characterization of a vertebrate GPI anchor and also the first demonstration of tissue specific differential glycosylation.
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene.
Tumor antigen is an antigenic substance produced in tumor cells, i.e., it triggers an immune response in the host. Tumor antigens are useful tumor markers in identifying tumor cells with diagnostic tests and are potential candidates for use in cancer therapy. The field of cancer immunology studies such topics.
Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently approved for human use.
According to the National Cancer Institute, a tumor antigen vaccine is a "vaccine made of cancer cells, parts of cancer cells, or pure tumor antigens ". A tumor antigen vaccine may stimulate the body's immune system to find and kill cancer cells. As such, tumor antigen vaccines are a type of cancer immunotherapy.
Melanocyte protein PMEL also known as premelanosome protein (PMEL) or silver locus protein homolog (SILV) is a protein that in humans is encoded by the PMEL gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1 gene.
Transmembrane glycoprotein NMB is a protein that in humans is encoded by the GPNMB gene. Two transcript variants encoding 560 and 572 amino acid isoforms have been characterized for this gene in humans. The mouse and rat orthologues of GPNMB are known as DC-HIL and Osteoactivin (OA), respectively.
Protein melan-A also known as melanoma antigen recognized by T cells 1 or MART-1 is a protein that in humans is encoded by the MLANA or "MALENA" gene. A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound by MHC class I complexes which present it to T cells of the immune system. These complexes can be found on the surface of melanoma cells. Decameric peptides (26-35) are being investigated as cancer vaccines.
Membrane-associated transporter protein (MATP), also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1, is a protein that in humans is encoded by the SLC45A2 gene.
Ocular albinism type 1(OA1) is the most common type of ocular albinism, with a prevalence rate of 1:50,000. It is an inheritable classical Mendelian type X-linked recessive disorder wherein the retinal pigment epithelium lacks pigment while hair and skin appear normal. Since it is usually an X-linked disorder, it occurs mostly in males, while females are carriers unless they are homozygous. About 60 missense and nonsense mutations, insertions, and deletions have been identified in Oa1. Mutations in OA1 have been linked to defective glycosylation and thus improper intracellular transportation.
Gp100:209-217(210M) is a synthetic peptide cancer vaccine consisting of amino acid residues 209 through 217 of the glycoprotein 100 (gp100) melanoma antigen, with a methionine substitution at position 210. It is often referred to as the gp100 cancer vaccine which can also include other peptides based on gp100.
Peptide-based synthetic vaccines, also called epitope vaccines, are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.
ALECSAT technology is a novel method of epigenetic cancer immunotherapy being used by the company CytoVac. It uses a patient's own immune system to target tumor cells in prostate cancer, glioblastomas, and potentially pancreatic cancer. ALECSAT research, directed by Alexei Kirken and Karine Dzhandzhugazyan, has led to several clinical trials.
T lymphocytes are cells of the immune system that attack and destroy virus-infected cells, tumor cells and cells from transplanted organs. This occurs because each T cell is endowed with a highly specific receptor that can bind to an antigen present at the surface of another cell. The T cell receptor binds to a complex formed by a surface protein named "MHC" and a small peptide of about 9 amino-acids, which is located in a groove of the MHC molecule. This peptide can originate from a protein that remains within the cell. Whereas each T cell recognizes a single antigen, collectively the T cells are endowed with a large diversity of receptors targeted at a wide variety of antigens. T cells originate in the thymus. There a process named central tolerance eliminates the T cells that have a receptor recognizing an antigen present on normal cells of the organism. This enables the T cells to eliminate cells with "foreign" or "abnormal" antigens without harming the normal cells.