The application, safety, and future of ex vivo immune cell therapies and prognosis in different malignancies

Introduction: Immunotherapy has revolutionized how cancer is treated. Many of these immunotherapies rely on ex vivo expansion of immune cells, classically T cells. Still, several immunological obstacles remain, including tumor impermeability by immune cells and the immunosuppressive nature of the tumor microenvironment (TME). Logistically, high costs of treatment and variable clinical responses have also plagued traditional T cell-based immunotherapies. Methods: To review the existing literature on cellular immunotherapy, the PubMed database was searched for publications using variations of the phrases "cancer immunotherapy", "ex vivo expansion", and "adoptive cell therapy". The Clinicaltrials.gov database was searched for clinical trials related to ex vivo cellular therapies using the same phrases. The National Comprehensive Cancer Network guidelines for cancer treatment were also referenced. Results: To circumvent the challenges of traditional T cell-based immunotherapies, researchers have developed newer therapies including tumor infiltrating lymphocyte (TIL), chimeric antigen receptor (CAR), T cell receptor (TCR) modified T cell, and antibody-armed T cell therapies. Additionally, newer immunotherapeutic strategies have used other immune cells, including natural killer (NK) and dendritic cells (DC), to modulate the T cell immune response to cancers. From a prognostic perspective, circulating tumor cells (CTC) have been used to predict cancer morbidity and mortality. Conclusion: This review highlights the mechanism and clinical utility of various types of ex vivo cellular therapies in the treatment of cancer. Comparing these therapies or using them in combination may lead to more individualized and less toxic chemotherapeutics.