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 In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...

targeting the folate receptor, which is overexpressed on certain cancers, such as

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

, and a potent chemotherapy drug,

vinblastine Vinblastine, sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder canc ...

. Vintafolide is designed to deliver the toxic vinblastine drug selectively to cells expressing the folate receptor using folate targeting. It is being developed with a companion imaging agent,

etarfolatide Technetium (99mTc) etarfolatide is an investigational non-invasive, folate receptor-targeting companion imaging agent that is being developed by Endocyte.''http://www.fiercemedicaldevices.com/story/endocytes-dx-spots-ovarian-and-lung-cancer-pa ...

, that identifies patients that express the folate receptor and thus would likely respond to the treatment with vintafolide. A Phase 3 study evaluating vintafolide for the treatment of platinum-resistant ovarian cancer (PROCEED trial) and a Phase 2b study(TARGET trial) in

non-small-cell lung carcinoma Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...

(NSCLC) are ongoing (in 2012). A Marketing Authorization Application (MAA) filing for vintafolide and etarfolatide for the treatment of patients with folate receptor-positive platinum-resistant

in combination with

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

, pegylated liposomal doxorubicin (PLD), has been accepted by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

. The drug received

orphan drug status An orphan drug is a pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by the condition ...

in Europe in March 2012. Merck & Co. acquired the development and marketing rights to this experimental cancer drug from Endocyte in April 2012. Endocyte remains responsible for the development and commercialization of etarfolatide, a non-invasive companion imaging agent used to identify patients expressing the folate receptor that will likely respond to treatment with vintafolide. In 2014 Merck and Endocyte stopped a late-stage study (PROCEED) of vintafolide in treating ovarian cancer on the recommendation of a data safety monitoring board, saying that the drug failed to improve progression-free survival.

Mechanism of action

Folate 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 ...

is required for cell division, and rapidly dividing

cancer cell Cancer cells are cells that divide continually, forming solid tumors or flooding the blood or lymph with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, an ...

s often express folate receptors in order to capture enough

folate 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 ...

to support rapid cell growth. Elevated expression of the folate receptor occurs in many diseases, including other aggressively growing

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s and

inflammatory disorders Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''d ...

. Vintafolide binds to the folate receptor and is subsequently taken up by the cell through a natural internalization process called

endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...

. Once inside the cell, vintafolide’s linker releases the

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

drug which kills the cell.

References

{{Intracellular chemotherapeutic agents Experimental cancer drugs Folates Small-molecule drug conjugates