First-in-human, first-in-class phase 1a study of BXQ-350 for solid tumors and gliomas.

Rixe, Olivier; Morris, John C.; Puduvalli, Vinay K.; Villanó, John L.; Wise‐Draper, Trisha M.; Muller, Carolyn; Johnson, Angela N.; Wesolowski, Robert; Qi, Xiaoyang

doi:10.1200/jco.2018.36.15_suppl.2517

Cited by 8 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, SapC-DOPS nanovesicles are capable of crossing the BBTB [10]. Phase I clinical trials for SapC-DOPS in patients with advanced solid tumors and recurrent highgrade gliomas have revealed an encouraging safety profile [24,25]. In conclusion, SapC-DOPS is a promising and selective PS-targeting treatment option for several cancers types, worthy of further investigation and clinical development.…”

Section: Discussionmentioning

confidence: 90%

“…A phase I clinical trial for SapC-DOPS (BXQ-350) was initiated in 2016 for patients with advanced solid tumors and recurrent high-grade gliomas. Phase 1a and 1b studies revealed an impressive safety profile and some efficacy even though treatment was started at very late stages of the disease [24,25]. Thus far, BXQ-350 has had no serious related adverse events in patients [25].…”

Section: Sapc-dops Clinical Trialmentioning

confidence: 99%

“…Specifically, our lab has focused on the development of SapC-DOPS, a PS-targeting nanovesicle comprised of saposin C (SapC; a lysosomal protein) and dioleylphosphatidylserine (DOPS) [2,10,12,15,17,22,23]. The unique appeal of SapC-DOPS as a cancer therapy include its consistent selective targeting and killing of cancer cells while being tolerated in healthy cellsthis phenomenon has been reflected in results of phase I clinical trials where SapC-DOPS showed a strong safety profile [24,25]. In addition, SapC-DOPS [1] utilizes multiple mechanisms to induce cancer cell death including caspase 9 cleavage and lysosomal membrane permeability [2] is capable of crossing the blood-brain tumor barrier and [3] enhances the effects of existing therapies [9,10,23,26].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

N’Guessan

Patel

2020

Cell Commun Signal

Self Cite

View full text Add to dashboard Cite

Phosphatidylserine (PS) is normally located in the inner leaflet of the membrane bilayer of healthy cells, however it is expressed at high levels on the surface of cancer cells. This has allowed for the development of selective therapeutic agents against cancer cells (without affecting healthy cells). SapC-DOPS is a PS-targeting nanovesicle which effectively targets and kills several cancer types including pancreatic, lung, brain, and pediatric tumors. Our studies have demonstrated that SapC-DOPS selectively induces apoptotic cell death in malignant and metastatic cells, whereas untransformed cells remain unaffected due to low surface PS expression. Furthermore, SapC-DOPS can be used in combination with standard therapies such as irradiation and chemotherapeutic drugs to significantly enhance the antitumor efficacy of these treatments. While the PS-targeting nanovesicles are a promising selective therapeutic option for the treatment of cancers, more preclinical studies are needed to fully understand the mechanisms leading to non-apoptotic PS expression on the surface of viable cancer cells and to determine the effectiveness of SapC-DOPS in advanced metastatic disease. In addition, the completion of clinical studies will determine therapeutic effects and drug safety in patients. A phase I clinical trial using SapC-DOPS has been completed on patients with solid tumors and has demonstrated compelling patient outcomes with a strong safety profile. Results from this study are informing future studies with SapC-DOPS.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Sapc-dops Clinical Trialmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

N’Guessan

Patel

2020

Cell Commun Signal

Self Cite

View full text Add to dashboard Cite

show abstract

“…While there is an initial weight loss, probably due to the radiation sickness all of the mice, regardless of treatment regimen, eventually lost about the same amount of weight, albeit at a later date for the 131 I-treated mice (data not shown). We have previously demonstrated that SapC-DOPS has limited toxicity both in mice [ 17 , 18 ] and humans [ 29 , 30 ]. In addition, we have used a structural analog of DiD, the fluorescent compound, CVM, to label SapC-DOPS in many studies and have not detected any change in behavior of mice treated with SapC-DOPS-CVM compared to unlabeled SapC-DOPS [ 18 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…SapC-DOPS specifically targets PS on the surface of tumor cells in this acidic milieu, leading to ceramide accumulation, caspase activation and eventual apoptosis [ 15 ], selectively killing GBM tumor cells, without apparent off-target toxicity to normal cells and tissues [ 26 , 27 , 28 ]. Indeed, SapC-DOPS has shown an exemplary safety profile in Phase I clinical trials [ 29 , 30 ]. A synergistic effect of SapC-DOPS and TMZ has been demonstrated for GBM in mice [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles

Davis

Vallabhapurapu

Chu

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM), a common type of brain cancer, has a very poor prognosis. In general, viable GBM cells exhibit elevated phosphatidylserine (PS) on their membrane surface compared to healthy cells. We have developed a drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), that selectively targets cancer cells by honing in on this surface PS. To examine whether SapC-DOPS, a stable, blood–brain barrier-penetrable nanovesicle, could be an effective delivery system for precise targeted therapy of radiation, we iodinated several carbocyanine-based fluorescent reporters with either stable iodine (127I) or radioactive isotopes (125I and 131I). While all of the compounds, when incorporated into the SapC-DOPS delivery system, were taken up by human GBM cell lines, we chose the two that best accumulated in the cells (DiI (22,3) and DiD (16,16)). Pharmacokinetics were conducted with 125I-labeled compounds and indicated that DiI (22,3)-SapC-DOPS had a time to peak in the blood of 0.66 h and an elimination half-life of 8.4 h. These values were 4 h and 11.5 h, respectively, for DiD (16,16)-SapC-DOPS. Adult nude mice with GBM cells implanted in their brains were treated with 131I-DID (16,16)-SapC-DOPS. Mice receiving the radionuclide survived nearly 50% longer than the control groups. These data suggest a potential novel, personalized treatment for a devastating brain disease.

show abstract

Actualité des essais thérapeutiques précoces au congrès de l’ASCO 2018 : nouveaux mécanismes, nouvelles cibles, nouvelles associations

et al. 2018

View full text Add to dashboard Cite

First-in-human, first-in-class phase 1a study of BXQ-350 for solid tumors and gliomas.

Cited by 8 publications

References 0 publications

SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles

Actualité des essais thérapeutiques précoces au congrès de l’ASCO 2018 : nouveaux mécanismes, nouvelles cibles, nouvelles associations

Contact Info

Product

Resources

About