A poster presentation by Corbus Pharmaceuticals Holdings at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Boston reveals new preclinical data for CRB-601.
An anti-αvβ8 integrin monoclonal antibody, CRB-601 is designed to block the activation of latent transforming growth factor β (TGFb) selectively within the tumor microenvironment.
The company said its latest preclinical data indicates significant tumor growth inhibition by CRB-601 as a single agent and in combination with anti-PD-1 treatment in the syngeneic murine tumor models MC38 and EMT6.
In addition, it found treatment with CRB-601 appears to restore sensitivity to checkpoint inhibitors in the Pan02 and 4T1 syngeneic tumor models, regarded as 'desert' tumors that are non-responsive to current CPIs.
“The ability of CRB-601 to significantly reduce the growth of tumors that are non-responsive to checkpoint inhibitors (CPIs) and to sensitize these tumors to CPI therapy continues to support our hypothesis that effective blockade of latent TGFβ activation should lead to enhanced immune cell invasion in the tumor microenvironment and augment the effects of anti-PD-1 therapy. The increased activity of CRB-601 in tumors expressing αvβ8 provides a promising biomarker for patient selection and stratification,” commented Rachael Brake, CSO, Corbus.
According to a study in the Journal of Cell Science, αvβ8 integrin is a receptor for ECM-bound forms of latent TGFβ proteins and promotes the activation of TGFβ signaling pathways. “Studies of the brain, lung and immune system reveal that the αvβ8 integrin-TGFβ axis mediates cell-cell contact and communication within complex multicellular structures. Perturbing components of this axis results in aberrant cell-cell adhesion and signaling leading to the initiation of various pathologies, including neurodegeneration, fibrosis, and cancer.”
T-cell memory response
Furthermore, the data indicates that tumor protection is associated with a durable T-cell memory response, said the developer.
Tumor-bearing mice initially rendered tumor-free by the combined treatment of CRB-601 + anti-PD-1 were subsequently reinoculated with the same tumor cells (MC38) and monitored for tumor establishment and growth. “After 30 days no tumors had formed in this cohort of animals, whereas implantation and eventual death occurred in 100% of the treatment naïve control animals. T-cell depletion studies indicated that protection against MC38 tumor growth in these rechallenged animals was dependent upon CD8+ T-cells,” reported Corbus.
The immunology company is currently developing CRB-601 as a potential treatment for solid tumor cancers; it says the program is on schedule for an IND submission in mid-2023.
