CELL INTELLIGENCE · 肿瘤细胞治疗研究

Lung cancer is the leading cause of all cancer-related deaths in the United States and remains a global health challenge. While targeted therapy has revolutionized the treatment landscape of nonsmall cell lung cancer, many patients lack actionable mutations. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), have significantly impacted outcomes in lung cancer in the last decade. Some patients, however, never respond or become refractory to ICIs. Newer therapies aimed at augmenting the immune system and enhancing antitumor effects are currently being explored. Adoptive cell therapy (ACT) employs T cells isolated from either tumors or peripheral blood and often engineers them to effect antitumor immune response. Chimeric antigen receptor T (CAR-T) cell therapy, engineered T cell receptor therapy, and tumor-infiltrating lymphocytes are examples of adoptive cellular therapies. CAR-T cell therapy has been successful in the treatment of hematological malignancies with several CAR products gaining approval in the treatment of refractory blood cancers. The success of ACTs in hematological cancers has fueled research into the role of these therapies in solid cancers including lung cancer. Many trials have had early promising results, with many clinical trials currently enrolling. There are many limitations to the efficacy of ACTs, as well as risks and benefits with the individual subtypes of ACT. With growing knowledge about tumor antigens and more advanced cell engineering, there is potential for ACT to result in durable responses in immunologically "cold" tumors. Here, we review the major subtypes of ACTs, evidence supporting their use in lung cancer, challenges, and future perspectives in ACTs. Additionally, we include T cell engagers and mRNA vaccine studies and potential combinatorial strategies in lung cancer. Adopting tomorrow s therapies today: a perspective review of immune cell therapies and mRNA vaccines targeting lung cancer cells Lung cancer is a prominent cause of cancer-related deaths in the United States and worldwide. Several approaches to treat lung cancer has been used over the years. We know that the immune system is not only designed to fight infections but also to recognize and kill cancer cells. A group of immune cells called killer T cells can bind to markers on the surface of cancerous cells. The understanding of the role the immune system plays in attacking cancer cells led to the development of immunotherapy. Immune checkpoint inhibitors are drugs that target proteins that act as off-switches in the immune system. Outcomes in lung cancer have improved with the introduction of immune checkpoint inhibitors, but still only a minority of patients have long term benefit. A new type of immunotherapy called adoptive cell therapy (ACT) is the focus of this perspective review. ACT is also referred to as cellular immunotherapy. This is an umbrella term including treatment that uses the cells of the immune system to get rid of cancer. There are different ways of utilizing ACT in the treatment of lung cancer. One way is to remove patient s immune cells and culture them in the laboratory. Additionally, there might be changes made to the genes of the patient s immune cells in the laboratory to boost their cancer-fighting abilities. Several clinical trials have demonstrated early promise, but these trials are still enrolling, and we have yet to fully understand how safe and effective these treatments are in lung cancer.