Phase I clinical trial of adoptive cellular immunotherapy with APN401 in patients with solid tumors

Triozzi, Pierre L.; Kooshki, Mitra; Alistar, Angela; Bitting, Rhonda L.; Neal, Amy; Lametschwandtner, Guenther; Loibner, Hans

doi:10.1186/2051-1426-3-s2-p175

Cited by 28 publications

(19 citation statements)

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“…A single intravenous infusion of APN401 into patients with resistant solid tumors is possible and safe. This result supported phase-II clinical trials of multiple infusions of APN401 [132].…”

Section: Clinical Trials Of Nano-sirna For Cancer Therapysupporting

confidence: 71%

Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

Kamaruzman

Aziz

Poh

et al. 2019

Cancers

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Overexpression of oncogenes and cross-talks of the oncoproteins-regulated signaling cascades with other intracellular pathways in breast cancer could lead to massive abnormal signaling with the consequence of tumorigenesis. The ability to identify the genes having vital roles in cancer development would give a promising therapeutics strategy in combating the disease. Genetic manipulations through siRNAs targeting the complementary sequence of the oncogenic mRNA in breast cancer is one of the promising approaches that can be harnessed to develop more efficient treatments for breast cancer. In this review, we highlighted the effects of major signaling pathways stimulated by oncogene products on breast tumorigenesis and discussed the potential therapeutic strategies for targeted delivery of siRNAs with nanoparticles in suppressing the stimulated signaling pathways.

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Section: Clinical Trials Of Nano-sirna For Cancer Therapysupporting

confidence: 71%

Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

Kamaruzman

Aziz

Poh

et al. 2019

Cancers

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“…Recently, it has been shown in a phase I trial that the strategy of silencing Cblb in human peripheral blood mononuclear cells followed by adoptive cell transfer is feasible and safe [53]. …”

Section: Discussionmentioning

confidence: 99%

Cblb-deficient T cells are less susceptible to PD-L1-mediated inhibition

2017

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Modulation of the immune system for the treatment of primary and metastatic tumors has been a goal of cancer research for many years. The E3 ubiquitin ligase Cbl-b has been established as an intracellular checkpoint that limits T cell activation, critically contributing to the maintenance of self-tolerance. Furthermore, it has been shown that Cblb deficiency enhances T cell effector functions towards tumors. Blockade of the immune checkpoints CTLA-4 and PD-1/PD-L1 has recently emerged as a promising strategy in the development of effective cancer immune therapies. Therefore, we explored the concept of targeting different checkpoints concomitantly. Interestingly, we observed that CTLA-4 but not PD-L1 based immunotherapy selectively enhanced the anti-tumor phenotype of Cblb-deficient mice. In agreement with the in vivo results, in vitro experiments showed that Cblb−/− T cells were less susceptible to PD-L1-mediated suppression of T cell proliferation and IFNγ secretion. Taken together, our findings reveal a so far unappreciated function of Cbl-b in the regulation of PD-1 signaling in murine T cells.

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“… 75 – 77 Because of the enhanced activation and antitumor responses of Cbl-b-deficient T cells, Cbl-b has become a focus for understanding the mechanisms of antitumor immunity and an attractive cancer immunotherapy target being exploited in preclinical studies and clinical trials. 78 , 79 Another E3 ubiquitin ligase Grail (RNF128) has been shown to negatively regulate T cell activation and maintain T cell anergy and tolerance. 80 , 81 Grail inhibits TCR-proximal signaling by targeting CD3ζ for ubiquitin-dependent degradation of CD3ζ, and Grail deficiency impairs T cell tolerance and sensitizes mice for autoimmune diseases 82 (Fig.…”

Section: Tcr Signalingmentioning

confidence: 99%

Targeting ubiquitin signaling for cancer immunotherapy

Zhou

Sun

2021

Sig Transduct Target Ther

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Cancer immunotherapy has become an attractive approach of cancer treatment with tremendous success in treating various advanced malignancies. The development and clinical application of immune checkpoint inhibitors represent one of the most extraordinary accomplishments in cancer immunotherapy. In addition, considerable progress is being made in understanding the mechanism of antitumor immunity and characterizing novel targets for developing additional therapeutic approaches. One active area of investigation is protein ubiquitination, a post-translational mechanism of protein modification that regulates the function of diverse immune cells in antitumor immunity. Accumulating studies suggest that E3 ubiquitin ligases and deubiquitinases form a family of potential targets to be exploited for enhancing antitumor immunity in cancer immunotherapy.

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Phase I clinical trial of adoptive cellular immunotherapy with APN401 in patients with solid tumors

Cited by 28 publications

References 0 publications

Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

Cblb-deficient T cells are less susceptible to PD-L1-mediated inhibition

Targeting ubiquitin signaling for cancer immunotherapy

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