Immunotherapy of Neuroendocrine Neoplasms: Any Role for the Chimeric Antigen Receptor T Cells?

SIMPLE SUMMARY: Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors arising in different organs whose clinical course is variable according to histological differentiation and metastatic spread. Therapeutic options have recently expanded, but there is a need for new effective therapies, especially in less differentiated forms. Chimeric antigen receptor T cells (CAR-T) have shown efficacy in several cancers, mainly hematological, but data on NENs are scattered. We aimed to analyze the available preclinical and clinical data about CAR-T in NENs, to highlight their potential role in clinical practice. A significant therapeutic effect of CAR-T cells in NENs emerges from preclinical studies. Results from clinical trials are expected in order to define their effective role in these cancers. ABSTRACT: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with variable clinical presentation and prognosis. Surgery, when feasible, is the most effective and often curative treatment. However, NENs are frequently locally advanced or already metastatic at diagnosis. Consequently, additional local or systemic therapeutic approaches are required. Immunotherapy, based on chimeric antigen receptor T cells (CAR-T), is showing impressive results in several cancer treatments. The aim of this narrative review is to analyze the available data about the use of CAR-T in NENs, including studies in both preclinical and clinical settings. We performed an extensive search for relevant data sources, comprising full-published articles, abstracts from international meetings, and worldwide registered clinical trials. Preclinical studies performed on both cell lines and animal models indicate a significant therapeutic effect of CAR-T cells in NENs. Ongoing and future clinical trials will clarify the possible role of these drugs in patients with highly aggressive NENs.