Lung cancer is one of the most common cancers worldwide and the leading cause of cancer-related deaths.
Lung cancer can be categorised into various, including ‘non-small cell carcinoma’ (NSCLC) and ‘small cell carcinoma’ (SCLC). NSCLC is more common (approximately 85% of tumours) and grows slowly, while SCLC is less common (approximately 15% of tumours) but often grows faster.
Treatments for lung cancer include surgery, chemotherapy, radiation therapy, targeted therapy drugs, and immunotherapy. If the cancer has been detected and treated early. the 5-year relative survival rate is about 65% for NSCLC. However, patients often present with advanced disease stages which significantly lowers the chances for successful treatment as the cancer has most likely spread to other organs. Therefore, early detection is key to increasing survival rates. A low-dose computed tomography scan (LDCT) can detect malignancies at early stages when they can be successfully treated. Furthermore, there is a pressing need for new therapies and targeted therapies and immunotherapies are showing great promise for increasing the life expectancy of patients.
Targeted treatments identify and attack cancer cells’ specific genes, proteins, or tumour microenvironment (TME). An example is epidermal growth factor receptor (EGFR) inhibitors which are inhibiting the growth of lung cancer cells with EGFR-specific mutations. Results from the ADAURA trial, showing that a daily dose of the EGFR-inhibitor osimertinib significantly increased the 5-year survival rate for early-stage (stage II to IIIA) NSCLC patients with a mutation in the EGFR were met with excitement when published this year in the New England Journal of Medicine.
These advanced treatments for lung cancer still have limitations, providing a window of opportunity for novel approaches, including CAR T cell therapy.
CAR T-cell therapy has been successfully applied for the treatment of B-cell malignancies. Since 2017 the FDA has approved six CAR T-cell products to treat selected blood cancers. Unfortunately, this success could not be replicated in patients with solid tumors and no approved CAR T cell therapies exist for lung cancer. Some of the challenges include the selection of specific tumor-associated antigens (TAA), an immunosuppressive TME and off-target toxicity due to target expression in healthy tissue.
TAAs that have been selected for CAR T cells include EGFR, MUC 1, DLL3, ROR1 and MSLN and screening of patients would be required to identify the most effective therapeutic approach. Expression of immune checkpoint inhibitors or cytokines by CAR T cells has been used in pre-clinical models to overcome the immunosuppressive TME and enhanced anti-tumour activity. CAR T cell therapy for lung cancer and other solid tumours is still in its infancy, but with the rapid progress in the field and new innovations, it is expected to become an important tool in the fight against lung cancer, especially in combination with established and new innovative therapeutic approaches.
Blog written by Dr. Frank Kirstein (PhD)
References
Masahiro Tsuboi, et al., Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med 2023; 389:137-147. DOI: 10.1056/NEJMoa2304594
https://clinicaltrials.gov/study/NCT02511106
https://www.cancer.gov/types/lung/research/nlst
Chen, L, et al. CAR-T cell therapy for lung cancer: Potential and perspective. Thorac Cancer. 2022; 13: 889– 899. https://doi.org/10.1111/1759-7714.14375
