Folate Receptor Beta as a Direct and Indirect Target for Antibody-Based Cancer Immunotherapy

Autor: Mathilde Poussin, Cheryl Nickerson-Nutter, Daniel J. Powell, Prannda Sharma, J. Michael Robinson, Alba Rodriguez-Garcia, A.G. Roy
Rok vydání: 2021
Předmět:
0301 basic medicine
Myeloid
THP-1 Cells
medicine.medical_treatment
Mice
SCID
folate receptor beta
Mice
Antineoplastic Agents
Immunological
0302 clinical medicine
Cancer immunotherapy
Mice
Inbred NOD
Medicine
Biology (General)
Spectroscopy
Mice
Knockout
Ovarian Neoplasms
Antibody-dependent cell-mediated cytotoxicity
education.field_of_study
tumor-associated macrophages
Myeloid leukemia
General Medicine
Neoplasm Proteins
Computer Science Applications
Leukemia
Myeloid
Acute
Chemistry
ovarian cancer
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Immunotherapy
QH301-705.5
HL-60 Cells
CHO Cells
acute myeloid leukemia
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Cricetulus
Animals
Humans
Folate Receptor 2
Physical and Theoretical Chemistry
education
QD1-999
Molecular Biology
Tumor microenvironment
Folate receptor beta
business.industry
Organic Chemistry
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Humanized mouse
Cancer research
business
Ovarian cancer
Zdroj: International Journal of Molecular Sciences; Volume 22; Issue 11; Pages: 5572
International Journal of Molecular Sciences, Vol 22, Iss 5572, p 5572 (2021)
International Journal of Molecular Sciences
ISSN: 1422-0067
Popis: Folate receptor beta (FRβ) is a folate binding receptor expressed on myeloid lineage hematopoietic cells. FRβ is commonly expressed at high levels on malignant blasts in patients with acute myeloid leukemia (AML), as well as on M2 polarized tumor-associated macrophages (TAMs) in the tumor microenvironment of many solid tumors. Therefore, FRβ is a potential target for both direct and indirect cancer therapy. We demonstrate that FRβ is expressed in both AML cell lines and patient-derived AML samples and that a high-affinity monoclonal antibody against FRβ (m909) has the ability to cause dose- and expression-dependent ADCC against these cells in vitro. Importantly, we find that administration of m909 has a significant impact on tumor growth in a humanized mouse model of AML. Surprisingly, m909 functions in vivo with and without the infusion of human NK cells as mediators of ADCC, suggesting potential involvement of mouse macrophages as effector cells. We also found that TAMs from primary ovarian ascites samples expressed appreciable levels of FRβ and that m909 has the ability to cause ADCC in these samples. These results indicate that the targeting of FRβ using m909 has the potential to limit the outgrowth of AML in vitro and in vivo. Additionally, m909 causes cytotoxicity to TAMs in the tumor microenvironment of ovarian cancer warranting further investigation of m909 and its derivatives as therapeutic agents in patients with FRβ-expressing cancers.
Databáze: OpenAIRE
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