Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model.

Background: Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve.

Methods: To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice.

Structure-guided engineering of the affinity and specificity of CARs against Tn-glycopeptides.

The potency of adoptive T cell therapies targeting the cell surface antigen CD19 has been demonstrated in hematopoietic cancers. It has been difficult to identify appropriate targets in nonhematopoietic tumors, but one class of antigens that have shown promise is aberrant O-glycoprotein epitopes. It has long been known that dysregulated synthesis of O-linked (threonine or serine) sugars occurs in many cancers, and that this can lead to the expression of cell surface proteins containing O-glycans comprised of a single -acetylgalactosamine (GalNAc, known as Tn antigen) rather than the normally extended carbohydrate.

Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with antineoplastic compounds.

Antineoplastic compounds are used in the treatment of a variety of cancers. The effectiveness of an antineoplastic compound to exert its activity is largely dependent on transport proteins involved in the entry of the compound into the cells, and those which drive it out of the cell. Organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), belonging to the SLCO family of proteins, are specifically expressed in the sinusoidal membranes of the liver, and are known to interact with a variety of drugs.

Interaction of human organic anion transporter 2 (OAT2) and sodium taurocholate cotransporting polypeptide (NTCP) with antineoplastic drugs.

The ability of an antineoplastic drug to exert its cytostatic effect depends largely on the balance between its uptake into and extrusion from the cancer cells. ATP driven efflux transporter proteins drive the export of antineoplastic drugs and play a pivotal role in the development of chemoresistance. As regards uptake transporters, comparably less is known on their impact in drug action.

Renal human organic anion transporter 3 increases the susceptibility of lymphoma cells to bendamustine uptake.

Chronic lymphatic leukemia (CLL) is often associated with nephritic syndrome. Effective treatment of CLL by chlorambucil and bendamustine leads to the restoration of renal function. In this contribution, we sought to elucidate the impact of organic anion transporters (OATs) on the uptake of bendamustine and chlorambucil as a probable reason for the superior efficacy of bendamustine over chlorambucil in the treatment of CLL.

HNF4α induced chemosensitivity to oxaliplatin and 5-FU mediated by OCT1 and CNT3 in renal cell carcinoma.

Increased expression of transporters-mediating uptake of antineoplastic drugs could render renal cell carcinoma (RCC) more sensitive to chemotherapy. Here, we studied the effect of hepatocyte nuclear factor 4α (HNF4α) on the expression of selected uptake transporters in RCC lines. Organic cation transporters (OCTs) and organic anion transporters (OATs) mRNA levels in HNF4α-transfected RCCs were measured by real-time PCR.