GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma

Bufalo, Francesca Del; Angelis, Biagio De; Caruana, Ignazio; Baldo, Giada Del; Ioris, Maria Antonietta De; Serra, Annalisa; Mastronuzzi, Angela; Cefalo, Maria Giuseppina; Pagliara, Daria; Amicucci, Matteo; Pira, Giuseppina Li; Leone, G; Bertaina, Valentina; Sinibaldi, Matilde; Cecca, Stefano Di; Guercio, Marika; Abbaszadeh, Zeinab; Iaffaldano, Laura; Gunetti, Monica; Iacovelli, Stefano; Bugianesi, Rossana; Macchia, Stefania; Algeri, Mattia; Merli, Pietro; Galaverna, Federica; Abbas, Rachid; Garganese, Maria Carmen; Villani, Maria Felicia; Colafati, Giovanna Stefania; Bonetti, F; Rabusin, Marco; Perruccio, Katia; Folsi, Veronica; Quintarelli, Concetta; Locatelli, Franco

doi:10.1056/nejmoa2210859

Cited by 147 publications

(51 citation statements)

References 32 publications

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“…On‐target off‐tumor effects are also a major safety concern for CAR‐T targeting the central nervous system (CNS). For example, CAR T cells targeting GD2, a ganglioside antigen expressed on the surface of several solid cancer such as neuroblastoma, glioma, cervical cancer, and sarcoma, showed good efficacy in clinical studies without significant safety concerns (Del Bufalo et al., 2023; Majzner et al., 2022). However, GD2 is also expressed at low levels in healthy neurons, skin melanocytes, and peripheral nerves (Doronin et al., 2014), increasing the risk of CNS toxicity.…”

Section: Preclinical Applications Of Humanized Mice For Cancer Immuno...mentioning

confidence: 99%

Humanized Mouse Models for Immuno‐oncology Drug Discovery

Kumari¹,

Feuer²,

Bourré³

2023

Current Protocols

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Breakthroughs in cancer treatment with immunotherapeutics have provided long‐term patient benefits for many different types of cancer. However, complete response is not achieved in many patients and tumor types, and the mechanisms underlying this lack of response are poorly understood. Despite this, numerous new targets, therapeutics, and drug combinations are being developed and tested in clinical trials. Preclinical models that recapitulate the complex human tumor microenvironment and the interplay between tumor and immune cells within the cancer‐immunity cycle are needed to improve our understanding and screen new therapeutics for efficacy and safety/toxicity. Humanized mice, encompassing human tumors and human immune cells engrafted on immunodeficient mice, have been widely used for many years in immuno‐oncology, with developments to improve both the humanization and the translational value central to the next generation of models. In this overview, we discuss recent advances in humanized models relevant to immuno‐oncology drug discovery, the advantages and limitations of such models, the application of humanized models for efficacy and safety assessments of immunotherapeutics, and the potential opportunities. © 2023 Crown Bioscience. Current Protocols published by Wiley Periodicals LLC.

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Section: Preclinical Applications Of Humanized Mice For Cancer Immuno...mentioning

confidence: 99%

Humanized Mouse Models for Immuno‐oncology Drug Discovery

Kumari¹,

Feuer²,

Bourré³

2023

Current Protocols

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“…Thousands of patients have now been treated in real‐world clinical practice, and this number is expected to increase substantially as randomized controlled trials establish a role for CAR‐T cells in earlier lines of therapy 11–14 . Promising breakthroughs in the treatment of solid organ malignancies and autoimmune diseases raise hope that CAR‐T cell therapy may play an even broader role in the future 15,16 . CAR‐T cell therapy is associated with well‐known early toxicities including cytokine release syndrome (CRS), immune effector cell‐associated neurotoxicity syndrome (ICANS), and immune effector‐cell associated hemophagocytic lymphohistiocytosis‐like syndrome (IEC‐HS), the assessment and management of which have been thoroughly described in consensus guidelines by the American Society for Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT), National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO) 17–21 .…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14] Promising breakthroughs in the treatment of solid organ malignancies and autoimmune diseases raise hope that CAR-T cell therapy may play an even broader role in the future. 15,16 CAR-T cell therapy is associated with well-known early toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effectorcell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), the assessment and management of which have been thoroughly described in consensus guidelines by the American Society for Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT), National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO). [17][18][19][20][21] However, comparatively less is known about the late effects of CAR-T cell therapy, an issue of growing importance given the rapidly increasing number of long-term survivors.…”

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confidence: 99%

Long‐term survivorship care after CAR‐T cell therapy

Puckrin,

Jamani,

Jimenez‐Zepeda

2023

European J of Haematology

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While cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome are well‐recognized acute toxicities of chimeric antigen receptor (CAR) T cell therapy, these complications have become increasingly manageable by protocolized treatment algorithms incorporating the early administration of tocilizumab and corticosteroids. As CAR‐T cell therapy expands to new disease indications and the number of long‐term survivors steadily increases, there is growing recognition of the need to appropriately evaluate and manage the late effects of CAR‐T cell therapy, including late‐onset or persistent neurotoxicity, prolonged cytopenias, delayed immune reconstitution and infections, subsequent malignancies, organ dysfunction, psychological distress, and fertility implications. In this review, we provide a practical approach to the long‐term survivorship care of the CAR‐T cell recipient, with a focus on the optimal strategies to address the common and challenging late complications affecting this unique population.

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“…Tackling these issues, particularly in solid tumors, is the clinical frontier for synthetic immunology, 16 and the lessons learned in this arena can pave the way for applications in other disease contexts. Some success of phase 1 trials of CAR T cells in solid tumors have been reported, 17–19 providing hope that engineered cell therapy can be effective in solid tumors, but currently these results are the exception. Our review seeks to identify obstacles learned from both preclinical experiments and clinical trials, describe the major remaining hurdles and current synthetic immunology approaches to overcome them, and propose a set of guidelines for successful translation of synthetic immunology from bench to bedside.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13][14][15] Tackling these issues, particularly in solid tumors, is the clinical frontier for synthetic immunology, 16 and the lessons learned in this arena can pave the way for applications in other disease contexts. Some success of phase 1 trials of CAR T cells in solid tumors have been reported, [17][18][19] providing hope that engineered cell therapy can be effective in solid tumors, but currently these results are the exception.…”

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confidence: 99%

Toward the clinical development of synthetic immunity to cancer

Garcia

Burnett

Roybal

2023

Immunological Reviews

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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.

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GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma

Cited by 147 publications

References 32 publications

Humanized Mouse Models for Immuno‐oncology Drug Discovery

Humanized Mouse Models for Immuno‐oncology Drug Discovery

Long‐term survivorship care after CAR‐T cell therapy

Toward the clinical development of synthetic immunity to cancer

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