CAR‐T cell therapy for lung cancer: Potential and perspective

Abstract

Lung cancer is the highest incidence and mortality of all cancers around the world. In the present immunotherapy era, an increasing number of immunotherapeutic agents including monoclonal antibody-targeted drugs have been used in the clinical treatment of malignancy, but it still has many limitations. Chimeric antigen receptormodified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have not only been used successfully against hematological tumors, but have also opened up new avenues for immunotherapy of solid tumors, including lung cancer. However, targeting lung cancer-specific antigens using engineered CAR-T cells is complicated by the lack of proper tumor-specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, along with off-target effect, etc. Simultaneously, the clinical application of CAR-T cells remains limited because of many challenges such as tumor lysis syndrome, neurotoxicity syndrome, and cytokine release syndrome. In this review, we outline the basic structure and generation characteristic of CAR-T cells and summarize the common tumorassociated antigens in clinical trials of CAR-T cell therapy for lung cancer, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for the pre-clinical experiments and clinical trials of CAR-T cell therapy in lung cancer. K E Y W O R D S chimeric antigen receptor-modified T cellsimmunotherapylung cancersolid tumortargeting specific antigens

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

“…According to the literature, CAR-T cells' most common targeted antigens in NSCLC are EGFR, MSLN, CEA, PD-L1, ROR1, B7H3, MUC1, HER2, and Delta-like ligand 3 (DLL3) [177,[198][199][200][201][202][203][204] (Fig. 3).…”

Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

“…Although CAR-T-cell therapies have achieved great success in hematological malignancies, the study of lung cancer is still in the early exploration stage. Numerous clinical trials have progressed slowly and have achieved very limited efficacy, and several challenges and hurdles remain, such as on-target/off-tumor toxicity, CAR-T cell trafficking and infiltration into the tumor, TME heterogeneity, immune suppression, and cytokine release syndrome (224)(225)(226). Recently, Vasic et al (227) found that allogeneic double-negative CAR-T cells inhibit tumor growth with no off-tumor toxicity in either a lung cancer xenograft model or B-cell acute lymphoblastic leukemia (B-ALL) was observed.…”

Nano-immunotherapy for lung cancer

“…Lung cancer treatments include surgery, chemotherapy, radiotherapy, immunotherapy, neoadjuvant therapy, etc. However, only 20% of patients are suitable for surgery and 80% experience recurrence and eventually die postoperatively [5]. Growing evidence has illustrated that immunotherapy, especially monoclonal antibody-targeted drugs, has been increasingly used in the clinical treatment of lung cancer, among the multifaceted treatment strategies [6].…”

“…Growing evidence has illustrated that immunotherapy, especially monoclonal antibody-targeted drugs, has been increasingly used in the clinical treatment of lung cancer, among the multifaceted treatment strategies [6]. In recent years, chimeric antigen receptor-modified T cells (CAR-T cells), as one of the emerging treatment strategies for cancer immunotherapy, have become a new hot spot and focus in the field of cancer therapy research [5,7]. Recently, personalized vaccines that individually select antigens for each patient are being developed [8].…”