Chemotactic cytokines or Chemokines bind to G protein-coupled receptors and mediate a wide range of biological functions, such as leukocyte adhesion and extravasation. There is a strong relation between tumour cell expression of certain Chemokine receptors and cancer progression, metastasis development and poor prognosis.
Chemokine Receptor 9, CCR9, is naturally expressed in the thymus and the crypts of the small bowel, but it is also overexpressed by CD4+ T-helper cells in T-cell Acute Lymphoblastic Leukaemia (T-ALL), while its expression in normal T-helper cells is rare and low. CCR9 ligand, CCL25, enhances leukemic T-cell proliferation.
CCR9 overexpression has been demonstrated in several tumor types including T-ALL, pancreatic cancer and ovary cancer.
CCR9 overexpression in T-ALL is associated to increased metastatic potential and tumor chemoresistance (Quiping et al. 2003, Tu et al. 2016).
CCR9 expression in solid tumors has been shown to exert immuno-modulatory effects on T-cell responses (Khandelwal et al. 2015).
CCR9 Program. Scientific Evidence
CCR9 is overexpressed in different blood neoplasia patients
- Analysis in blood or bone marrow samples, from patients suffering from different types of blood neoplasia has shown CCR9 overexpression in up to 80% of the patients analyzed, including T-ALL and Non-Hodgkin Lymphoma.
CCR9 as a novel target in solid tumors
- CCR9 has been proposed as a promising immuno-oncology target in different solid tumors.
- CCR9 overexpression is associated with highly metastatic stages of pancreatic cancer.
- Soluble CCR9 overexpression is associated to invasive stages in certain solid tumors including breast, lung, and ovary cancer.
Anti-CCR9 Therapeutic Antibodies
SunRock,in collaboration with CIB-CSIC, has developed anti-CCR9 humanized antibodies that show ADCC and CDC-driven antitumor activity, both in vitro and in vivo, with improved affinity to a new and exclusive human CCR9 epitope.
Mice tumors treated with anti-CCR9 antibodies showed increased apoptosis and necrosis and reduced angiogenesis and cell proliferation (Chamorro et al. 2014, Somovilla-Crespo et al. 2018).
SunRock Biopharma owns exclusive, world-wide rights of the IP protecting the CCR9-targeted antibodies.
SunRock’s lead asset, SRB1, is a first-in-class anti-CCR9 antibody, which has shown high efficacy to treat T-ALL and pancreatic cancer in preclinical models.
SRB1 showed in vivo Efficacy: T-ALL Circulating Cell Model
- Complete tumor regression in T-ALL models.
- Increased survival rate compared with standard of care chemotherapeutics.
- No toxicity symptoms in any of the animal models tested.
SRB1 (hematologic tumors)
SRB1 (solid tumors)