About this Research Topic
In this Research Topic, state-of-the-art multi-signal integration designs are discussed in a series of excellent papers that not only review the subject but also describe advances in this promising area of translational science. By modifying effector cells with variants of natural immune receptors, cell therapies have been created that have remarkable specificity for cancer cells and minimize the collateral damage to normal tissues. The basis for the selectivity is the application of receptor systems that can recognize antigen profiles, rather than single antigens. Recent advances include OR gates with either two activating receptors or a single receptor with dual-binding, AND gates with two receptors that act in concert such that two antigens are required to induce cytotoxicity, and NOT gates that generally incorporate one activating receptor and one inhibitory receptor. A variety of strategies to overcome the technical hurdles associated with these approaches, including CRISPR and synthetic mRNA, are described. Comparison to protein therapeutics-based logic gate approaches, that seek to achieve similar cancer cell specificity through multi-specific large molecule-mediated activation of endogenous immune cells, will also be covered.
We are interested in manuscripts that address any of the following topics:
1. Multi-targeted gene-edited immune cells (e.g., T cells, NK cells, macrophages) designed to react to more than one antigen in a gated fashion
2. Novel concepts for multi-antigen-targeted cell therapy for cancer or inflammation
3. Methods of modification that are transient (e.g., using synthetic mRNA)
4. Comparisons between different multi-targeting modalities: e.g., different effector cell types or cell vs. multi-specific large molecules
5. Comparisons between in vivo and ex vivo methods for multi-antigen-targeted cell therapy
6. Identifying optimal tumor-associated antigen combinations to enable multi-targeted approaches
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Keywords: Cell therapy, Logic gate, OR gate, AND gate, NOT gate, Oncology, inflammation, Multi-specific large molecules
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.