Optimizing CARs for ocular delivery

Nellan, Anandani; Fry, Terry J.

doi:10.1038/s43018-020-00127-y

Cited by 2 publications

(1 citation statement)

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“…The authors demonstrated that IL-15 increases the proliferation and persistence of GD2 CAR T cells and that subretinal delivery of CAR T cells within a hydrogel completely controls RB in immunocompromised mice, with no obvious damage to the surrounding retina [41]. Thus, in addition to the eye's being well suited for localized delivery of CAR T cells for accessibility reasons, ocular delivery may be a scenario in which allogeneic products may not be rejected and therefore may be more feasible than delivery at other sites [42]. A recent study has demonstrated dysregulated immune cell infiltrates in RB.…”

Section: Immunotherapy: Chimeric Antigen Receptor T-cell Therapy and ...mentioning

confidence: 99%

Emerging New Therapeutics for Retinoblastoma

2022

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Background: Over the last few decades, chemotherapy has become the main treatment of retinoblastoma, delivered through various routes: intravenous (IVC), intra-arterial (IAC), and intravitreal (IvitC). Despite its efficacy, chemotherapy related toxicity (ocular and systemic) and recurrences due to resistant tumor clones are common, highlighting the need for novel therapeutic agents. Summary: Recent advances in our understanding of the molecular drivers of Rb1 tumorigenesis and mechanisms of tumor resistance have afforded opportunities to explore novel targets such as the MDMX–p53 pathway (Nutlin-3), Histone deacetylase inhibitors (HDACi), Spleen tyrosine kinase (SYK) inhibitors, and genetic and immune modulatory drugs. In this review we discuss the limitations of current therapeutic strategies, candidate cellular pathways, current evidence for newer targeted drugs, and offer a look towards the future. Key messages: Advances in the understanding of the molecular drivers of RB pathway have provided opportunities to explore novel drugs with targeted effects, improved bioavailability, and reduced chemotoxicity.

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Section: Immunotherapy: Chimeric Antigen Receptor T-cell Therapy and ...mentioning

confidence: 99%