AERIO news in brief

Remodeling Tumor Immunogenicity with Dual-Activatable Binary CRISPR Nanomedicine for Cancer Immunotherapy

“…Cancer immunotherapy, which activates a patient’s immune system to combat cancer cells, has demonstrated its potential in long-term inhibition of tumor growth, metastasis, and recurrence. , The first and foremost challenge to be addressed in activating antitumor immunity is the specific recognition of tumor cells by the body’s immune system. , Tumor cells present tumor-associated antigens (TAAs) on their surface mainly through major histocompatibility complex class I (MHC-I), which could be efficiently recognized by cytotoxic T lymphocytes (CTLs) for tumor elimination . However, recent studies have revealed that MHC-1 expression on the surface of tumor cells gradually decreases with tumor growth, resulting in insufficient TAAs presentation and immune evasion. , Apart from decreased MHC-1 expression, the immune recognition of tumor cells is also limited by overexpressed immune checkpoints. − For example, programmed death ligand 1 (PD-L1) on the surface of multiple tumor cells can bind with programmed death 1 (PD-1) expressed by CTLs, leading to inactivation and exhaustion of CTLs. , As a result, most tumors are not immunogenic enough to initiate and maintain adequate antitumor immune responses. − …”

“…8−11 For example, programmed death ligand 1 (PD-L1) on the surface of multiple tumor cells can bind with programmed death 1 (PD-1) expressed by CTLs, leading to inactivation and exhaustion of CTLs. 12,13 As a result, most tumors are not immunogenic enough to initiate and maintain adequate antitumor immune responses. 14−16 To date, several potential drugs, including small molecule inhibitors, antibodies, and small interfering RNAs (siRNAs), are under investigation or have been used clinically for targeting MHC-1 and PD-L1.…”