Phase I study of PT-112, a novel pyrophosphate-platinum immunogenic cell death inducer, in advanced solid tumours

Karp, Daniel D.; Camidge, D. Ross; Infante, J.; Ames, Tyler D.; Price, Matthew R.; Jimeno, J.; Bryce, Alan H.

doi:10.1016/j.eclinm.2022.101430

Cited by 22 publications

(22 citation statements)

References 21 publications

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“…The worldwide market size of magnesium citrate is projected to reach US$ 50 million by 2025 with a compound annual growth rate (CAGR) of 3.4% during the period 2021–2025 . Anhydrous magnesium citrate (Mg 3 (C 6 H 5 O 7 ) 2 ) and magnesium citrate nonahydrate (Mg 3 (C 6 H 5 O 7 ) 2 ·9H 2 O) are the two common types of magnesium citrate with global consumptions of approx.…”

Section: Introductionmentioning

confidence: 99%

Magnesium Citrate Powders from Waste Bitterns via Crystallization and Spray Drying

Luong

Wang

Zurrer

et al. 2022

Ind. Eng. Chem. Res.

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The pilot-scale production of two magnesium citrate products, using a waste bittern discharged from a salt work as the raw material, was conducted in this study. Magnesium citrate nonahydrate and anhydrous magnesium citrate were prepared via crystallization and spray drying techniques, respectively, and characterized for purity, crystalline structure, particle shape, particle size distribution, and other properties. The material and energy costs were estimated based on technical data obtained from the pilot trials in conjunction with specific energy consumption of equivalent industrial-scale equipment. The costs were used to evaluate and compare the economic feasibility of both processes on a commercial scale. Although the material and energy costs at US$ 924 and US$ 33–81 per tonne, respectively, required to make magnesium citrate nonahydrate are lower than for anhydrous magnesium citrate at US$ 1256 and US$ 141 per tonne, respectively, the higher market price of anhydrous magnesium citrate at US$ 5000 per tonne compared to US$ 3000 per tonne for the hydrated form suggests production via spray drying is potentially the more profitable approach.

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Section: Introductionmentioning

confidence: 99%

Magnesium Citrate Powders from Waste Bitterns via Crystallization and Spray Drying

Luong

Wang

Zurrer

et al. 2022

Ind. Eng. Chem. Res.

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“…[2][3][4][5] Besides mediating cytostatic and cytotoxic effects in numerous human and mouse cancer cells, PT-112 elicits various danger signals that are linked to immunogenic cell death (ICD), such as calreticulin exposure, as well as ATP and HMGB1 secretion. 3,6,7 Accordingly, mouse cancer cells succumbing to PT-112 in vitro efficiently protect immunocompetent, tumor-naïve mice from challenge with living cancer cells of the same type. 6,7 Moreover, PT-112 synergizes with PD-1 or PD-L1 blockade to control mouse tumors developing in immunologically competent hosts.…”

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confidence: 99%

“…3,6,7 Accordingly, mouse cancer cells succumbing to PT-112 in vitro efficiently protect immunocompetent, tumor-naïve mice from challenge with living cancer cells of the same type. 6,7 Moreover, PT-112 synergizes with PD-1 or PD-L1 blockade to control mouse tumors developing in immunologically competent hosts. 6,7 In some tumor models, robust type I interferon (IFN) signaling is required for ICD [8][9][10] However, the role of type I IFN signaling in the immunogenicity of PT-112 remains unclear.…”

mentioning

confidence: 99%

“…6,7 Moreover, PT-112 synergizes with PD-1 or PD-L1 blockade to control mouse tumors developing in immunologically competent hosts. 6,7 In some tumor models, robust type I interferon (IFN) signaling is required for ICD [8][9][10] However, the role of type I IFN signaling in the immunogenicity of PT-112 remains unclear. Methods We used wild-type, mitochondrial DNA (mtDNA) depleted (rho 0 ), as well as Casp2 -/and Casp3 -/mouse TS/A cells.…”

mentioning

confidence: 99%

“…13,14 In line with this possibility, both Casp2 -/and Casp3 -/-TS/A cells exhibited increased cytosolic mtDNA accumulation upon PT-112 treatment. As PT-112 is a potent inducer of ICD in vaccination assays 6,7 CASP3 activation elicited during the cytotoxic response to PT-112 may not influence the ability of PT-112 to drive prophylactic anticancer immunity in tumor-naïve hosts. Additional studies with established tumor models are needed to clarify the impact of caspases on the immunogenicity of PT-112 in clinically relevant settings.…”

mentioning

confidence: 99%

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1118 Immunologically relevant effects of PT-112 on cancer cell mitochondria

Yamazaki

Galluzzi

Yim

et al. 2022

Regular and Young Investigator Award Abstracts

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Immunogenic Cell Death in Hematological Malignancy Therapy

Liu

et al. 2023

Advanced Science

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Although the curative effect of hematological malignancies has been improved in recent years, relapse or drug resistance of hematological malignancies will eventually recur. Furthermore, the microenvironment disorder is an important mechanism in the pathogenesis of hematological malignancies. Immunogenic cell death (ICD) is a unique mechanism of regulated cell death (RCD) that triggers an intact antigen‐specific adaptive immune response by firing a set of danger signals or damage‐associated molecular patterns (DAMPs), which is an immunotherapeutic modality with the potential for the treatment of hematological malignancies. This review summarizes the existing knowledge about the induction of ICD in hematological malignancies and the current research on combining ICD inducers with other treatment strategies for hematological malignancies.

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Phase I study of PT-112, a novel pyrophosphate-platinum immunogenic cell death inducer, in advanced solid tumours

Cited by 22 publications

References 21 publications

Magnesium Citrate Powders from Waste Bitterns via Crystallization and Spray Drying

Magnesium Citrate Powders from Waste Bitterns via Crystallization and Spray Drying

1118 Immunologically relevant effects of PT-112 on cancer cell mitochondria

Immunogenic Cell Death in Hematological Malignancy Therapy

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