Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors

Gururangan, Sridharan; Sayour, Elias Elias; Mitchell, Duane A.

doi:10.20517/2347-8659.2018.44

Cited by 5 publications

(5 citation statements)

References 105 publications

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“…and i.d.) Medulloblastoma, neuroectodermal tumor NCT01326104 (I, II) None 2010 Active, not recruiting [ 36 ] Total tumor mRNA, ex vivo expanded lymphocytes, GM-CSF and td Diffuse intrinsic pontine glioma, Brain stem glioma NCT03396575 (I) Cyclophosphamide + fludarabine lymphodepleting conditioning or temozolomide 2018 Recruiting Universitair Ziekenhuis Brussel, Bart Nens MAGE-A3, MAGE-C2, tyrosinase and gp100 mRNA, co-electroporated with TriMix (CD70, CD40L, caTLR4) mRNA Melanoma NCT01302496 (II, single arm) Ipilimumab (antagonistic anti-CTLA-4) 2011 Completed [ 37 – 39 ] Melanoma NCT01676779 (II, randomized) None 2012 Completed [ 39 ] Direct injection of mRNA BioNTech SE RNA-LPX with NY-ESO-1, MAGE-A3, tyrosinase and TPTE (i.v.) Advanced melanoma NCT02410733 (I) None 2015 Active, not recruiting [ 40 , 41 ] RNA-LPX with TNBC TAAs, p53 and neoAgs (warehouse) (i.v.)…”

Section: Mrna-based Cancer Vaccinesmentioning

confidence: 99%

mRNA therapeutics in cancer immunotherapy

et al. 2021

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Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Nucleoside modification and elimination of double-stranded RNA can reduce the immunomodulatory activity of mRNA and increase and prolong protein production. In combination with nanoparticle-based formulations that increase transfection efficiency and facilitate lymphatic system targeting, nucleoside-modified mRNA enables efficient delivery of cytokines, costimulatory receptors, or therapeutic antibodies. Steady but transient production of the encoded bioactive molecule from the mRNA template can improve the pharmacokinetic, pharmacodynamic and safety properties as compared to the respective recombinant proteins. This may be harnessed for applications that benefit from a higher level of expression control, such as chimeric antigen receptor (CAR)-modified adoptive T-cell therapies. This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.

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Section: Mrna-based Cancer Vaccinesmentioning

confidence: 99%

mRNA therapeutics in cancer immunotherapy

et al. 2021

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“…Thirty‐two prospective clinical trials comprising 984 patients with advanced solid tumors who had also undergone mRNA vaccines either as monotherapies or as combined choices were included in the meta‐analysis (Figure 1). The trials were published from 2002 to 2023 and the characteristics and findings of these trials were expressed in Table 1 4,9–38 . These clinical trials consisted of 15 phases 1, 11 phases I/II, 5 phase II, and 1 phase III trial.…”

Section: Resultsmentioning

confidence: 99%

“…The trials were published from 2002 to 2023 and the characteristics and findings of these trials were expressed in Table 1 . 4 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 These clinical trials consisted of 15 phases 1, 11 phases I/II, 5 phase II, and 1 phase III trial. There were 680 males (69.1%) and 304 females (30.9%).…”

Section: Resultsmentioning

confidence: 99%

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Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta‐analysis

Zhang

Zheng

et al. 2023

MedComm

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Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1‐year/2‐year progression‐free survival [PFS], and overall survival [OS]) and safety (vaccine‐related grade 3–5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non‐small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6–17.0%) and 34.6% (95%CI, 24.1–45.9%). The estimates for 1‐year and 2‐year PFS were 38.4% (95%CI, 24.8−53.0%) and 20.0% (95%CI, 10.4–31.7%), respectively. The estimates for 1‐year and 2‐year OS were 75.3% (95%CI, 62.4–86.3%) and 45.5% (95%CI, 34.0–57.2%), respectively. The estimate for vaccine‐related grade 3–5 AEs was 1.0% (95%CI, 0.2–2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3–5 AEs.

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“…Intracellular domain composed of CD3ζ to direct T cells for performing the primary cytolytic activity. However, cytotoxic T cells require further signaling when they encounter a cognate foreign antigen to induce expansion, persistence, and cytokine secretion ( 21 ). To address this issue, 2 nd and 3 rd generation of CAR T cells developed with the 2 nd generation composed of co-stimulatory domains such as CD28, 4-1BB to improve proliferation and cytokine production of CAR T cells.…”

Section: Exogenous T Cells For Gbmmentioning

confidence: 99%

Optimizing T Cell-Based Therapy for Glioblastoma

et al. 2021

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Evading T cell surveillance is a hallmark of cancer. Patients with solid tissue malignancy, such as glioblastoma (GBM), have multiple forms of immune dysfunction, including defective T cell function. T cell dysfunction is exacerbated by standard treatment strategies such as steroids, chemotherapy, and radiation. Reinvigoration of T cell responses can be achieved by utilizing adoptively transferred T cells, including CAR T cells. However, these cells are at risk for depletion and dysfunction as well. This review will discuss adoptive T cell transfer strategies and methods to avoid T cell dysfunction for the treatment of brain cancer.

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Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors

Abstract: How to cite this article: Gururangan S, Sayour E, Mitchell DA. Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors.

Cited by 5 publications

References 105 publications

mRNA therapeutics in cancer immunotherapy

mRNA therapeutics in cancer immunotherapy

Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta‐analysis

Optimizing T Cell-Based Therapy for Glioblastoma

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