Toward the clinical development of synthetic immunity to cancer

Abstract

SummarySynthetic biology (synbio) tools, such as chimeric antigen receptors (CARs), have been designed to target, activate, and improve immune cell responses to tumors. These therapies have demonstrated an ability to cure patients with blood cancers. However, there are significant challenges to designing, testing, and efficiently translating these complex cell therapies for patients who do not respond or have immune refractory solid tumors. The rapid progress of synbio tools for cell therapy, particularly for cancer immunotherapy, is encouraging but our development process should be tailored to increase translational success. Particularly, next‐generation cell therapies should be rooted in basic immunology, tested in more predictive preclinical models, engineered for potency with the right balance of safety, educated by clinical findings, and multi‐faceted to combat a range of suppressive mechanisms. Here, we lay out five principles for engineering future cell therapies to increase the probability of clinical impact, and in the context of these principles, we provide an overview of the current state of synbio cell therapy design for cancer. Although these principles are anchored in engineering immune cells for cancer therapy, we posit that they can help guide translational synbio research for broad impact in other disease indications with high unmet need.

NETosis: Sculpting tumor metastasis and immunotherapy

“…12 Immunosurveillance of cancer cells mainly relies upon NK and cytotoxic T-cell populations, notably killing targeted cells following the polarized release of cytotoxic granule proteins. 159,160 The two cell populations involve diverse immune escape mechanisms that evolve over time and cause immune cells to disarm, or sequester, from pathological lesions. Immune checkpoint blockade overcomes the immunosuppressive state of the TME and enhances antigenspecific cytotoxic immunity.…”