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ADC Development for FOLR1 Targets

Recently, folate receptor alpha (FOLR1) has attracted extensive attention in the field of cancer research. As a membrane-bound protein, FOLR1 has high affinity for binding folate and transporting it into cells. Compared with normal tissues, elevated levels of FOLR1 in tumor cells make it an ideal target for cancer therapy. The targeted delivery of potent cytotoxic molecules into cancer cells is considered a promising anticancer strategy. With years of experience in bioconjugation and chemical development, BOC Sciences offers a extensive range of ADC preparation services for FOLR1 Targets.

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Introduction of FOLR1 Targets

FOLR1 is a glycosylphosphatidylinositol (GPI)-anchored membrane protein and shows a high affinity for binding and coordinating the transport of the folate, which is an essential vitamin required in large quantities by almost all cells. Studies have shown that the FOLR1 receptor mediates folate transportation through receptor-mediated endocytosis upon ligand binding. Furthermore, the differential overexpression in malignant tissues and the discovery of methods for the non-destructive introduction of proteins utilizing FOLR1-mediated endocytosis of folate has led to its evaluation as a potential therapeutic target for FOLR1-expressing tumors.

The three types of folate transporters Fig. 1. The three types of folate transporters (Trends in Endocrinology & Metabolism. 2022, 33(3): 159-174).

Clinical ADC Therapy Targeting FOLR1

The tumor specificity of FOLR1 makes it an important target for tumor diagnosis and cancer therapy. Currently, several types of folate receptor-targeted therapies have been developed and are in various stages of clinical trials for the treatment of ovarian and lung cancer, such as antibodies and folate-drug conjugates. MORAb-202 is a FOLR1-targeting ADC drug, which is coupled by farletuzumab antibody and eribulin payload through cathepsin-cleavable linker. Preclinical characterization analysis showed that MORAb-202 exhibited excellent biochemical properties and cytotoxicity with a 4:1 drug to antibody ratio. Besides, studies have shown that MORAb-202 targets FOLR1-expressing cell lines and produces durable responses in FOLR1-expressing xenograft models. Currently, MORAb-202 is being developed in a Phase I clinical study in patients with advanced solid tumors that express FOLR1.

Our FOLR1-targeted ADC Development Services (Include but are not limited to the followings)

FOLR1 Targeted Therapy in Ovarian Cancer

Ovarian carcinomas account for the highest mortality among all gynecological cancers in the world. It is hypothesized that FOLR1 upregulation in solid malignancies is due to the increased metabolic requirements for folates to fuel nucleic acid synthesis and cellular growth. The biological relevance of folates to carcinogenesis has thus made FOLR1 an attractive therapeutic target in ovarian cancer, especially those of epithelial etiology, where FOLR1 is upregulated in approximately 90% of the cases.

FOLR1 Targeted Therapy in Gastric Cancer

Gastric cancer is one of the most malignant cancers, with an especially high incidence in East Asia. Chemotherapy is the main treatment for gastric cancer, but it is less efficient and has systemic toxicity because of its nonspecific antitumor effects. FOLR1 can be a key immunotherapy target against gastric cancer because more than one-third of patients with gastric cancer have FOLR1 expression.

FOLR1 Targeted Therapy in Breast Cancer

Breast cancer represents a heterogeneous group of human cancer at both histological and molecular levels. Traditionally, breast cancer was evaluated upon the tumor characteristics such as its histopathologic type, grade, size, lymph nodal status and distant metastasis. Several studies in breast cancer suggest that FOLR1 may also represent an important therapeutic target in primary breast cancers.

What Can We Do for You?

BOC Sciences is a service provider in ADC-related pharmaceuticals and chemicals. We provide comprehensive ADC development services for FOLR1-targeted therapy. Our indications mainly include ovariancancer, gastric cancer, breast cancer and non-small cell lung cancer, etc. Our leading bioconjugation programs can help customers access the best ADC candidates. If you are interested in our ADC-related services for FOLR1-targets, please click here for more information.

References

  1. Leung, F. et al. Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients. Clinical biochemistry. 2013, 46(15): 1462-1468.
  2. Kim, M. et al. Folate receptor 1 (FOLR1) targeted chimeric antigen receptor (CAR) T cells for the treatment of gastric cancer. PloS one. 2018, 13(6): e0198347.
  3. Necela, B.M. et al. Folate receptor-α (FOLR1) expression and function in triple negative tumors. PloS one. 2015, 10(3): e0122209.
  4. Matsunaga, Y. et al. Novel Anti-FOLR1 Antibody–Drug Conjugate MORAb-202 in Breast Cancer and Non-Small Cell Lung Cancer Cells. Antibodies. 2021, 10(1): 6.
ADC Development for Targets
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