The glycoprotein FRα is a membrane-attached transport protein that is shielded from the immune system in healthy cells. However, it is upregulated in various malignancies, involved in cancer development and is also immunogenic. Furthermore, FRα is a tumor-associated antigen endowed with unique properties, thus rendering it a suitable target for immunotherapeutic development in cancer. Various anti- FRα immunotherapeutic strategies are thus currently being developed and clinically assessed for the treatment of various solid tumors. These approaches include passive anti-FRα immunotherapies, such as monoclonal antibodies, or active immunotherapies, such as CART, folate haptens and vaccines. In this review, we will explore the advances in the field of FRα-based immune therapies and discuss both their successes and shortcomings in the clinical setting.
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http://dx.doi.org/10.1016/j.cytogfr.2019.02.001 | DOI Listing |
Front Immunol
May 2022
Department of Chemistry, Purdue Institute for Drug Discovery and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
Pharmaceutics
June 2021
Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
Messenger RNA (mRNA) is not an attractive candidate for gene therapy due to its instability and has therefore received little attention. Recent studies show the advantage of mRNA over DNA, especially in cancer immunotherapy and vaccine development. This study aimed to formulate folic-acid-(FA)-modified, poly-amidoamine-generation-5 (PAMAM G5D)-grafted gold nanoparticles (AuNPs) and to evaluate their cytotoxicity and transgene expression using the luciferase reporter gene (F-mRNA) in vitro.
View Article and Find Full Text PDFCancer Res
February 2021
Department of Chemistry, Purdue University, West Lafayette, Indiana.
Although immunotherapies of tumors have demonstrated promise for altering the progression of malignancies, immunotherapies have been limited by an immunosuppressive tumor microenvironment (TME) that prevents infiltrating immune cells from performing their anticancer functions. Prominent among immunosuppressive cells are myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that inhibit T cells via release of immunosuppressive cytokines and engagement of checkpoint receptors. Here, we explore the properties of MDSCs and TAMs from freshly isolated mouse and human tumors and find that an immunosuppressive subset of these cells can be distinguished from the nonimmunosuppressive population by its upregulation of folate receptor beta (FRβ) within the TME and its restriction to the TME.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2019
Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
Systemic messenger RNA (mRNA) delivery, although still in its infancy, holds immense potential for application in cancer vaccination and immunotherapy. Its advantages over DNA transfection make it attractive in applications where transient expression is desired. However, this has proved challenging due to mRNA's instability and susceptibility to degradation.
View Article and Find Full Text PDFCytokine Growth Factor Rev
February 2019
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA. Electronic address:
The glycoprotein FRα is a membrane-attached transport protein that is shielded from the immune system in healthy cells. However, it is upregulated in various malignancies, involved in cancer development and is also immunogenic. Furthermore, FRα is a tumor-associated antigen endowed with unique properties, thus rendering it a suitable target for immunotherapeutic development in cancer.
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