Chimeric Antigen Receptor (CAR)-T-Cell Therapy exert an immune response against non-small-cell lung cancer (NSCLC). As novel agents of immunotherapy, CAR-T cells target specific antigens in NSCLC.
Let us summarize the common tumor-associated antigens targeted in clinical trials on CAR-T-cell therapy for NSCLC:
The most effective therapies for NSCLC are:
The combination of nivolumab plus ipilimumab yielded more favorable results in patients with advanced NSCLC expressing programmed death-ligand 1 (PD-L1).
Modified-T-cell therapy, particularly using chimeric antigen receptor (CAR)-T cells, has attracted growing interest in recent years
Tyrosine kinase inhibitors serve as clinical therapy for metastatic NSCLC patients harboring epidermal growth factor receptor (EGFR).
Anti-CD19 CAR-T cells are approved by the US Food and Drug Administration for the treatment of hematological B-cell malignancies. Recent progress indicates that CAR-T-cell therapy is also a promising strategy for the treatment of NSCLC in clinical trials
Anti-CD19 CAR-T-cell therapy caused selection of pre-existing variants of CD19 altering the target epitope beyond recognition by the CAR and this mechanics allow to overcome the risk of tumor antigen escape in immune-based anti-tumor therapies, including for NSCLC.
As a novel strategy for the treatment of NSCLC, CAR-T cell therapy has undergone great progress and has entered a stage of rapid development but certain arms are needed to be unraveled in future
Sudden and more rapid therapeutic effect on NSCLC than conventional treatment does is associated with toxicity which needs to be studied in trials.
Indeed, CARs have overcome the initial limitations of cancer therapy, but are currently limited by other tumor escape methods that are why these CARs are being studied in both animal models and clinical trials in the attempt to mitigate tumor antigen heterogeneity.
As we discussed many obstacles remain in the application of CAR-T-cell therapy in NSCLC, especially the heterogeneity of antigens expressed by tumor cells. The next steps is to better identify patients with a primary or acquired risk of resistance to CAR-T-cell therapy.
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