Vintafolide—targeting the folate receptor with a cytotoxic offers hope

Recruiting cytotoxic T cells to folate-receptor-positive cancer cells.

One new class of biologics that is generating a great deal of interest as next-generation cancer therapeutics are bispecific antibodies that simultaneously target the cluster of differentiation 3 (CD3) protein and tumor-associated antigens to recruit cytotoxic T cells from the patient s own immune system to eliminate cancer cells. Examples include the first approved bispecific antibody in Europ...

Private company offers hope to cancer patients--for a price.

UMSCC38 cells amplified at 11q13 for the folate receptor synthesize a mutant nonfunctional folate receptor.

Some cells accumulate folate via a receptor-coupled process termed potocytosis. The folate receptor, a glycosyl phosphatidylinositol anchored M(r) 38,000-39,000 glycoprotein, is coded for by at least two genes (FR alpha and FR beta) at 11q13. The karyotype of UMSCC38, a human squamous cell carcinoma cell line, suggests that it may contain multiple copies of the folate receptor gene(s). Southern...

Site-specific folate conjugation to a cytotoxic protein.

Conjugation to folic acid is known to enhance the uptake of molecules by human cells that over-produce folate receptors. Variants of bovine pancreatic ribonuclease (RNase A) that have attenuated affinity for the endogenous ribonuclease inhibitor protein (RI) are toxic to mammalian cells. Here, the random acylation of amino groups in wild-type RNase A with folic acid is shown to decrease its cat...

Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria.

Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic pr...