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Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division and maturation of blood cells. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.
A radioligand is a microscopic particle which consists of a therapeutic radioactive isotope and the cell-targeting compound - the ligand. The ligand is the target binding site, it may be on the surface of the targeted cancer cell for therapeutic purposes. Radioisotopes can occur naturally or be synthesized and produced in a cyclotron/nuclear reactor. The different types of radioisotopes include Y-90, H-3, C-11, Lu-177, Ac-225, Ra-223, In-111, I-131, I-125, etc. Thus, radioligands must be produced in special nuclear reactors for the radioisotope to remain stable. Radioligands can be used to analyze/characterize receptors, to perform binding assays, to help in diagnostic imaging, and to provide targeted cancer therapy. Radiation is a novel method of treating cancer and is effective in short distances along with being unique/personalizable and causing minimal harm to normal surrounding cells. Furthermore, radioligand binding can provide information about receptor-ligand interactions in vitro and in vivo. Choosing the right radioligand for the desired application is important. The radioligand must be radiochemically pure, stable, and demonstrate a high degree of selectivity, and high affinity for their target.
Sulfamethoxazole is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as Escherichia coli and Listeria monocytogenes.
In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga-PSMA is used for cancer imaging. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET).
TAH molecule, also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.
Copper-64 (64Cu) is a positron and beta emitting isotope of copper, with applications for molecular radiotherapy and positron emission tomography. Its unusually long half-life (12.7-hours) for a positron-emitting isotope makes it increasingly useful when attached to various ligands, for PET and PET-CT scanning.
Folate targeting is a method utilized in biotechnology for drug delivery purposes. This Trojan Horse process, which was created by Drs. Christopher P. Leamon and Philip S. Low, involves the attachment of the vitamin, folate, to a molecule/drug to form a "folate conjugate". Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates also bind tightly to the FR and trigger cellular uptake via endocytosis. Molecules as diverse as small radiodiagnostic imaging agents to large DNA plasmid formulations have successfully been delivered inside FR-positive cells and tissues.
Vintafolide is an investigational targeted cancer therapeutic currently under development by Endocyte and Merck & Co. It is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor, which is overexpressed on certain cancers, such as ovarian cancer, and a potent chemotherapy drug, vinblastine.
Small molecule drug conjugates or SMDCs are built with three modules: a targeting ligand, a linker and a drug payload. The targeting ligands consist of low molecular weight, high-affinity ligands that are precisely linked to potent drugs. The linkers are designed to be stable in the bloodstream and then release the active drug from the targeting ligand when the SMDC is taken up by the diseased cell. The drug payloads are highly active molecules that are too toxic to be administered in their untargeted forms at therapeutic dose levels. This modular approach allows varying targeting ligands, linker systems and drug payloads and generate SMDCs for different diseases. The most advanced SMDC is vintafolide, a derivative of the anti-mitotic chemotherapy drug vinblastine which is chemically linked to folic acid. Potent, bioactive natural products like triptolide that inhibit mammalian transcription has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.
Technetium (99mTc) etarfolatide is an investigational non-invasive, folate receptor-targeting companion imaging agent that is being developed by Endocyte. Etarfolatide consists of a small molecule targeting the folate receptor and an imaging agent, which is based on technetium-99m. This companion imaging agent identifies cells expressing the folate receptor, including cancer and inflammatory cells.
Seagen Inc. is an American biotechnology company focused on developing and commercializing innovative, empowered monoclonal antibody-based therapies for the treatment of cancer. The company, headquartered in Bothell, Washington, is the industry leader in antibody-drug conjugates or ADCs, a technology designed to harness the targeting ability of monoclonal antibodies to deliver cell-killing agents directly to cancer cells. Antibody-drug conjugates are intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy, while potentially enhancing antitumor activity.
Sutro Biopharma, Inc. is a publicly traded biotechnology company headquartered in South San Francisco, California focused on clinical-stage drug discovery, development and manufacturing. Using a proprietary cell-free protein synthesis platform, Sutro is working on oncology therapeutics using protein engineering and rational design. Founded in 2003 under the name Fundamental Applied Biology, the company name changed to Sutro Biopharma in 2009. William Newell, CEO as of 2024, joined Sutro in January 2009.
Advanced Accelerator Applications is a France-based pharmaceutical group, specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine to diagnose and treat serious conditions in the fields of oncology, neurology, cardiology, infectious and inflammatory diseases.
DMTHF-Tc is a radiopharmaceutical that combines DMTHF, a modified folate, with technetium-99m (99mTc), a gamma emitting radionuclide, in a chelate conjugate. It shows selectivity for certain cancer cells that overexpress FR-α, and can be used for diagnostic imaging in nuclear medicine. DMTHF-Tc was developed by the Philip Low lab at Purdue University.
A PSMA scan is a nuclear medicine imaging technique used in the diagnosis and staging of prostate cancer. It is carried out by injection of a radiopharmaceutical with a positron or gamma emitting radionuclide and a prostate-specific membrane antigen (PSMA) targeting ligand. After injection, imaging of positron emitters such as gallium-68 (68Ga), copper-64 (64Cu), and fluorine-18 (18F) is carried out with a positron emission tomography (PET) scanner. For gamma emitters such as technetium-99m (99mTc) and indium-111 (111In) single-photon emission computed tomography (SPECT) imaging is performed with a gamma camera.
Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11 sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.
Lutetium (177Lu) vipivotide tetraxetan, sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.
Immunoliposome therapy is a targeted drug delivery method that involves the use of liposomes coupled with monoclonal antibodies to deliver therapeutic agents to specific sites or tissues in the body. The antibody modified liposomes target tissue through cell-specific antibodies with the release of drugs contained within the assimilated liposomes. Immunoliposome aims to improve drug stability, personalize treatments, and increased drug efficacy. This form of therapy has been used to target specific cells, protecting the encapsulated drugs from degradation in order to enhance their stability, to facilitate sustained drug release and hence to advance current traditional cancer treatment.
References
- 1 2 3 4 5 6 7 Potera, Carol (April 2013). "Exploiting Folate Pathways to Treat Cancer: Endocyte Uses an Imaging Agent to Select Patients Likely to Respond to Its Therapies". Genetic Engineering & Biotechnology News. 33 (7): 12, 14. doi:10.1089/gen.33.7.03.
- ↑ "Clinical Trials Update", Genetic Engineering & Biotechnology News , 29 (8): 58, 2009
- ↑ Rapaport, Lisa; Spears, Lee (4 February 2011). "Drugmaker Endocyte Rises 29% After Initial Public Offering". Bloomberg.
- ↑ Taylor, Nick Paul (2018-10-18). "Novartis inks $2.1B Endocyte buyout, furthering radiotherapy push". Fierce Biotech. Retrieved 2022-04-13.
- ↑ "Endocyte's kidney conjugates get right to the spot - FiercePharma". www.fiercedrugdelivery.com.
- 1 2 "Endocyte soars on cancer drug deal with Merck". Reuters. 16 April 2012.
- ↑ Leamon, C. P.; Low, P. S. (1 July 1991). "Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis". Proceedings of the National Academy of Sciences. 88 (13): 5572–5576. Bibcode:1991PNAS...88.5572L. doi: 10.1073/pnas.88.13.5572 . PMC 51919 . PMID 2062838.
- ↑ Covello, Kelly; Flefleh, Christine; Menard, Krista; Wiebesiek, Amy; McGlinchey, Kelly; Wen, MeiLi; Westhouse, Richard; Reddy, Joe; Vlahov, Iontcho; Hunt, John; Rose, William; Leamon, Chris; Vite, Greg; Lee, Francis (1 May 2008). "Preclinical pharmacology of epothilone-folate conjugate BMS-753493, a tumor-targeting agent selected for clinical development". Cancer Research. 68 (9 Supplement): 2326.
- ↑ "Novartis to buy cancer drugmaker Endocyte for $2.1 billion in cash". Reuters. 18 October 2018. Archived from the original on November 28, 2018.
- ↑ Miller, John (18 October 2018). "Novartis pushes deeper into nuclear medicine with $2.1 billion deal". Reuters. Archived from the original on November 28, 2018.
- ↑ "Novartis announces planned acquisition of Endocyte to expand expertise in radiopharmaceuticals and build on commitment to transformational therapeutic platforms". Novartis.
