Arming T cells with C-X-C-motive receptor 6 enables adoptive T cell therapy of pancreatic cancer

Lesch, Stefanie; Blumenberg, Viktoria; Stoiber, Stefan; Ogonek, Justyna; Cadilha, Bruno L.; Dantes, Zahra; Rataj, Felicitas; Dorman, Klara; Lutz, Justina; Karches, Clara H.; Heise, Constanze; Grassmann, Simon; Megens, Remco T. A.; Ruehland, Svenja; Pilato, Mauro Di; Pruessmann, Jasper N.; Ormanns, Steffen; Reischer, Anna; Duewell, Peter; Schnurr, M.; Subklewe, Marion; Reichert, Maximilian; Mempel, TR; Endres, Stefan; Kobold, Sebastian

doi:10.1016/j.ejca.2019.01.080

Cited by 2 publications

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“…Thus, adoptive cell transfer therapy alone might not be sufficient to treat patients with cold and altered tumor profiles. To endow T cells with a more exceptional ability to migrate into tumors, different Review chemokine systems, including CCR4 (Di Stasi et al, 2009;Rapp et al, 2015), CXCR2 (Idorn et al, 2018;Jin et al, 2019;Peng et al, 2010), CX 3 CR1 (Siddiqui et al, 2016), and CXCR6 (Lesch et al, 2019), have been tested in the context of adoptive cell transfer therapy in mouse tumor models. However, the translation of these preclinical studies is urgently needed to determine if manipulation of the chemokine system can enhance the efficacy of adoptive cell transfer therapy for cancer patients.…”

Section: Role Of Chemokines In Cancer Treatmentmentioning

confidence: 99%

Chemokines and the immune response to cancer

2021

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Section: Role Of Chemokines In Cancer Treatmentmentioning

confidence: 99%

Chemokines and the immune response to cancer

2021

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“…70 In T cells, it has been reported that ectopic expression of GPCRs like CXCR1, CXCR2, CXCR6, or CCR4 can enhance migration and persistence of CAR T cells in tumor and augment therapeutic efficacy of CAR T cells. [71][72][73] Functional pairs of mutated GPCRs and nonendogenous ligands have great potential as synthetic tools to engineer T cells for cancer therapy. These engineered GPCRs and ligands are also called receptors activated solely by a synthetic ligand (RASSLs).…”

Section: Synthetic Receptor-ligand Pairsmentioning

confidence: 99%

Chimeric non-antigen receptors in T cell-based cancer therapy

Guo

Kent

Dávila

2021

J Immunother Cancer

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Adoptively transferred T cell-based cancer therapies have shown incredible promise in treatment of various cancers. So far therapeutic strategies using T cells have focused on manipulation of the antigen-recognition machinery itself, such as through selective expression of tumor-antigen specific T cell receptors or engineered antigen-recognition chimeric antigen receptors (CARs). While several CARs have been approved for treatment of hematopoietic malignancies, this kind of therapy has been less successful in the treatment of solid tumors, in part due to lack of suitable tumor-specific targets, the immunosuppressive tumor microenvironment, and the inability of adoptively transferred cells to maintain their therapeutic potentials. It is critical for therapeutic T cells to overcome immunosuppressive environmental triggers, mediating balanced antitumor immunity without causing unwanted inflammation or autoimmunity. To address these hurdles, chimeric receptors with distinct signaling properties are being engineered to function as allies of tumor antigen-specific receptors, modulating unique aspects of T cell function without directly binding to antigen themselves. In this review, we focus on the design and function of these chimeric non-antigen receptors, which fall into three broad categories: ‘inhibitory-to-stimulatory’ switch receptors that bind natural ligands, enhanced stimulatory receptors that interact with natural ligands, and synthetic receptor-ligand pairs. Our intent is to offer detailed descriptions that will help readers to understand the structure and function of these receptors, as well as inspire development of additional novel synthetic receptors to improve T cell-based cancer therapy.

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Arming T cells with C-X-C-motive receptor 6 enables adoptive T cell therapy of pancreatic cancer

Cited by 2 publications

References 0 publications

Chemokines and the immune response to cancer

Chemokines and the immune response to cancer

Chimeric non-antigen receptors in T cell-based cancer therapy

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