Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy

Fan, Jiaqi; Adams, Anne; Sieg, Noëlle; Heger, Jan‐Michel; Gödel, Philipp; Kutsch, Nadine; Kaul, David; Teichert, Marcel; Tresckow, Bastian von; Buecklein, Veit; Goesmann, Gretha; Li, Minglun; Struve, Nathalie; Trommer, Maike; Linde, Philipp; Rosenbrock, Johannes; Celik, Eren; Penack, Olaf; Stuschke, Martin; Subklewe, Marion; Belka, Claus; Bergwelt‐Baildon, Michael von; Borchmann, Peter; Marnitz, Simone; Baues, Christian

doi:10.1016/j.radonc.2023.109580

Cited by 17 publications

(16 citation statements)

References 24 publications

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“…75 Notably, there is evidence of synergy for irradiation with CAR T cells. 452 We recently demonstrated in a preclinical ovarian model that low doses of radiotherapy (LD-RT) which are non-toxic could trigger changes in the TME to reverse immune desertification, reprogram the myeloid compartment, and enable responsiveness to personalized combinatorial immunotherapy. 76 We are keen to explore LD-RT in combination with ACT as others have shown that it can help mitigate antigen escape to CAR therapy in a TRAIL-dependent manner.…”

Section: Amanda Lund Has Recently Demonstrated That Cxcr4 Expression Inmentioning

confidence: 99%

“…In addition, as we have previously reviewed, it is possible to combine T‐cell therapies with other forms of cancer treatments 75 . Notably, there is evidence of synergy for irradiation with CAR T cells 452 . We recently demonstrated in a preclinical ovarian model that low doses of radiotherapy (LD‐RT) which are non‐toxic could trigger changes in the TME to reverse immune desertification, reprogram the myeloid compartment, and enable responsiveness to personalized combinatorial immunotherapy 76 .…”

Section: Future Perspectivesmentioning

confidence: 99%

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Coengineering specificity, safety, and function into T cells for cancer immunotherapy

Giordano Attianese,

Ash,

Irving

2023

Immunological Reviews

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SummaryAdoptive T‐cell transfer (ACT) therapies, including of tumor infiltrating lymphocytes (TILs) and T cells gene‐modified to express either a T cell receptor (TCR) or a chimeric antigen receptor (CAR), have demonstrated clinical efficacy for a proportion of patients and cancer‐types. The field of ACT has been driven forward by the clinical success of CD19‐CAR therapy against various advanced B‐cell malignancies, including curative responses for some leukemia patients. However, relapse remains problematic, in particular for lymphoma. Moreover, for a variety of reasons, relative limited efficacy has been demonstrated for ACT of non‐hematological solid tumors. Indeed, in addition to pre‐infusion challenges including lymphocyte collection and manufacturing, ACT failure can be attributed to several biological processes post‐transfer including, (i) inefficient tumor trafficking, infiltration, expansion and retention, (ii) chronic antigen exposure coupled with insufficient costimulation resulting in T‐cell exhaustion, (iii) a range of barriers in the tumor microenvironment (TME) mediated by both tumor cells and suppressive immune infiltrate, (iv) tumor antigen heterogeneity and loss, or down‐regulation of antigen presentation machinery, (v) gain of tumor intrinsic mechanisms of resistance such as to apoptosis, and (vi) various forms of toxicity and other adverse events in patients. Affinity‐optimized TCRs can improve T‐cell function and innovative CAR designs as well as gene‐modification strategies can be used to coengineer specificity, safety, and function into T cells. Coengineering strategies can be designed not only to directly support the transferred T cells, but also to block suppressive barriers in the TME and harness endogenous innate and adaptive immunity. Here, we review a selection of the remarkable T‐cell coengineering strategies, including of tools, receptors, and gene‐cargo, that have been developed in recent years to augment tumor control by ACT, more and more of which are advancing to the clinic.

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Section: Amanda Lund Has Recently Demonstrated That Cxcr4 Expression Inmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Coengineering specificity, safety, and function into T cells for cancer immunotherapy

Giordano Attianese,

Ash,

Irving

2023

Immunological Reviews

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“…Some studies have shed light on the role of radiotherapy as bridging therapy (bRT). Preliminary evidence suggests that the combination of CAR-T therapy with bRT may enhance therapeutic bene ts, not only through local antineoplastic effects but also by local and possibly systemic immunomodulatory mechanisms [12,[20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed / refractory large B-cell lymphoma: findings from a German monocentric study.

Eigendorff,

Filimonova,

Scholl

et al. 2024

Preprint

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Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy. This single center analysis of tisagenlecleucel (tisa-cel) outcomes in the real world reveals response rates surpassing pivotal trials and other real-world reports. Analyzing 29 rr LBCL patients, the median age was 63, with a median of 3 prior treatments. Twenty patients (69%) were refractory to any systemic therapy before CAR-T cell treatment. Following leukapheresis, 25 patients (86%) received bridging therapy with the majority undergoing chemotherapy (52%) or combined modality therapy (32%). Radiotherapy (RT) was part of the bridging strategy in 44%, with moderately hypofractionated involved site RT (30.0 Gy/2.5 Gy) being applied most frequently (64%). Post-CAR-T infusion, the objective response rate at 30 days was 83%, with 55% achieving complete response. Twelve-month progression-free (PFS) and overall survival (OS) were 60% and 74%, respectively, with a median follow up of 11.1 months for PFS and 17.9 months for OS. Factors significantly associated with PFS were chemotherapy sensitivity pre-leukapheresis and response to bridging. The study underscores the importance of minimal tumor burden at CAR-T initiation, emphasizing the need for suitable bridging regimens. The findings advocate for clinical trials and further real-world analyses to optimize CAR-T cell therapy outcomes by identifying the most effective bridging strategies.

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“… 6 These strategies encompass further optimizing CAR structure, remodeling TME, 7 targeting inhibitors in TME (e.g., immune checkpoints, chemokine-receptor networks, and immunosuppressive cells), 8 combining immune checkpoint inhibitors, 9 , 10 combining chemotherapy, 11 and combining radiotherapy. 12 , 13 Currently, although CAR-T cells exhibit lower effectiveness in solid tumors compared to hematological malignancies, 14 it is anticipated that once these obstacles are overcome, CAR-T cells will undergo a significant advancement in the treatment of solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Miao,

Zhang,

et al. 2024

Human Vaccines & Immunotherapeutics

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CAR-T cell therapy has emerged as a significant approach for the management of hematological malignancies. Over the past few years, the utilization of CAR-T cells in the investigation and treatment of solid tumors has gained momentum, thereby establishing itself as a prominent area of research. This descriptive study involved the retrieval of articles about CAR-T cell therapy for solid tumors from the Web of Science Core Collection (WoSCC) database. Subsequently, bibliometric analysis and knowledge map analysis were conducted on these articles. The field under consideration is currently experiencing a period of swift advancement, as evidenced by the escalating number of publications in this domain each year. The United States holds an indisputable position as the foremost leader in this particular field, with the University of Pennsylvania emerging as the most active institution. The authors with the highest citation frequency and co-citation frequency are Carl H. June and Shannon L. Maude, respectively. The research hotspots in this field mainly focus on five aspects. Additionally, 10 emerging themes were identified. This study undertakes a comprehensive, systematic, and objective analysis and exploration of the field of CAR-T cell treatment for solid tumors, utilizing bibliometric methods. The findings of this study are expected to serve as a valuable reference and enlightenment for future research endeavors in this particular domain.

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Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy

Cited by 17 publications

References 24 publications

Coengineering specificity, safety, and function into T cells for cancer immunotherapy

Coengineering specificity, safety, and function into T cells for cancer immunotherapy

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed / refractory large B-cell lymphoma: findings from a German monocentric study.

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

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