mRNA-Based Therapy for NSCLC
Non-small cell lung cancer (NSCLC), the most common cause of cancer-related death, has a poor prognosis and currently has no cure. The diagnosis and treatment of NSCLC have been hindered to some extent due to the heterogeneous nature of this disease. Fortunately, the latest developments in emerging treatments (including immunotherapy) have brought hope for the treatment of NSCLC. In addition to the immune checkpoint inhibitors (ICIs), the current major immunotherapeutic strategies, mRNA-based therapy as a new modality is applied for the treatment of NSCLC. Creative Biogene is a forward-looking research institute as well as a leading custom service provider in mRNA-based drug research and development (R&D). Our team is experienced in the customized synthesis of mRNA, mRNA optimization, and mRNA delivery system development. We are devoted to offering high-quality service and achieving the best outcome for our customers from all over the world.
Non-small cell lung cancer (NSCLC)—the most common type of lung cancer
Lung cancer is the major cause of cancer death and the second most common malignancy reported worldwide. The total number of deaths caused by lung cancer is greater than that of breast, colon, and prostate cancer combined. A prospective evaluation of the incidence trend revealed that the appearance of lung cancer is related to environmental and genetic factors, especially the habit of smoking. According to the WHO, lung cancer can be mainly classified into two types, including Small Cell Lung Cancer (SCLC, approximately 20% of all lung cancer cases) and NSCLC (accounting for 80% of all lung cancer cases). The outcome of NSCLC is usually poor because approximately 30–40% of patients presented with tumor migration to other organs, such as the bones or the brain.
Treatment of NSCLC
To treat NSCLC, different available strategies have been developed. These methods can be classified into conventional therapies and emerging treatments. Here, we summarize existing strategies for the treatment of NSCLC. In particular, it is important for treatment to consider a patient's disease status, clinical condition, and tumor histological cell type on an individualized basis.
Treatments of NSCLC.
mRNA-based drugs for NSCLC
Progress in mRNA-based technology in terms of mRNA structural improvements (such as codon optimizations, nucleotide modifications, and chemical synthesis of higher-order cap structures, etc.) and efficient mRNA delivery vehicles (including lipid nanoparticles (LNPs), polymers, peptides, etc.) might pave the way for mRNAs to enter various therapeutic applications. In recent, mRNA-based therapy as a new modality (antigen-specific vaccination approach) is applied for NSCLC treatment. The administration of antigen-specific mRNA can activate protective humoral and cellular immune responses against one or more tumor-associated antigens (TAAs) without adding substantial toxicity. Antigen-specific immunotherapy CV9201 is one of the most promising vaccines available. It is composed of full-length mRNAs encoding multiple, indication-specific, NSCLC tumor-associated antigens (including NY-ESO-1, MAGE-C1, MAGE-C2, surviving, and 5T4) complexed with protamine. The selection of these antigens is based on their role in NSCLC oncogenesis, ability to induce cytotoxic lymphocytes and/or antigen-specific antibodies, and differential expression between malignant and normal tissues. In addition, CV9202 is another active cancer immunotherapeutic that induces targeted immune responses, which comprises protamine-formulated, sequence-optimized mRNA encoding six NSCLC TAAs (including NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1). Study treatment was feasible and well-tolerated, supporting further investigation of mRNA-based immunotherapy in NSCLC.
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- García-Fernández, C., et al. (2020). "Nanomedicine in Non-Small Cell Lung Cancer: From Conventional Treatments to Immunotherapy." Cancers, 12(6), 1609.
- Sebastian, M., et al. (2019). "A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer." Cancer Immunology, Immunotherapy, 68(5), 799-812.