Tags

Type your tag names separated by a space and hit enter

Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases.
Neurooncol Adv. 2020 Jan-Dec; 2(1):vdaa052.NA

Abstract

Background

Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of the cerebrospinal fluid (CSF). Here, we examine the in vitro use of neurapheresis therapy as a novel, adjunctive treatment option for LM by filtering cells and augmenting the distribution of drugs that may have the potential to enhance the current clinical approach.

Methods

Clinically relevant concentrations of VX2 carcinoma cells were suspended in artificial CSF. The neurapheresis system's ability to clear VX2 carcinoma cells was tested with and without the chemotherapeutic presence (methotrexate [MTX]). The VX2 cell concentration following each filtration cycle and the number of cycles required to reach the limit of detection were calculated. The ability of neurapheresis therapy to circulate, distribute, and maintain therapeutic levels of MTX was assessed using a cranial-spinal model of the SAS. The distribution of a 6 mg dose was monitored for 48 h. An MTX-specific ELISA measured drug concentration at ventricular, cervical, and lumbar sites in the model over time.

Results

In vitro filtration of VX2 cancer cells with neurapheresis therapy alone resulted in a 2.3-log reduction in cancer cell concentration in 7.5 h and a 2.4-log reduction in live-cancer cell concentration in 7.5 h when used with MTX. Cranial-spinal model experiments demonstrated the ability of neurapheresis therapy to enhance the circulation of MTX in CSF along the neuraxis.

Conclusion

Neurapheresis has the potential to act as an adjunct therapy for LM patients and significantly improve the standard of care.

Authors+Show Affiliations

Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.Minnetronix Neuro, Inc., St. Paul, Minnesota, USA.Minnetronix Neuro, Inc., St. Paul, Minnesota, USA.Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32642705

Citation

Ejikeme, Tiffany, et al. "Evaluation of Neurapheresis Therapy in Vitro: a Novel Approach for the Treatment of Leptomeningeal Metastases." Neuro-oncology Advances, vol. 2, no. 1, 2020, pp. vdaa052.
Ejikeme T, de Castro GC, Ripple K, et al. Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases. Neurooncol Adv. 2020;2(1):vdaa052.
Ejikeme, T., de Castro, G. C., Ripple, K., Chen, Y., Giamberardino, C., Bartuska, A., Smilnak, G., Marius, C., Boua, J. V., Chongsathidkiet, P., Hodges, S., Pagadala, P., Verbick, L. Z., McCabe, A. R., & Lad, S. P. (2020). Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases. Neuro-oncology Advances, 2(1), vdaa052. https://doi.org/10.1093/noajnl/vdaa052
Ejikeme T, et al. Evaluation of Neurapheresis Therapy in Vitro: a Novel Approach for the Treatment of Leptomeningeal Metastases. Neurooncol Adv. 2020 Jan-Dec;2(1):vdaa052. PubMed PMID: 32642705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases. AU - Ejikeme,Tiffany, AU - de Castro,George C, AU - Ripple,Katelyn, AU - Chen,Yutong, AU - Giamberardino,Charles, AU - Bartuska,Andrew, AU - Smilnak,Gordon, AU - Marius,Choiselle, AU - Boua,Jane-Valeriane, AU - Chongsathidkiet,Pakawat, AU - Hodges,Sarah, AU - Pagadala,Promila, AU - Verbick,Laura Zitella, AU - McCabe,Aaron R, AU - Lad,Shivanand P, Y1 - 2020/04/18/ PY - 2020/7/10/entrez PY - 2020/7/10/pubmed PY - 2020/7/10/medline KW - Neurapheresis KW - VX2 KW - leptomeningeal metastases KW - methotrexate KW - subarachnoid space SP - vdaa052 EP - vdaa052 JF - Neuro-oncology advances JO - Neurooncol Adv VL - 2 IS - 1 N2 - Background: Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of the cerebrospinal fluid (CSF). Here, we examine the in vitro use of neurapheresis therapy as a novel, adjunctive treatment option for LM by filtering cells and augmenting the distribution of drugs that may have the potential to enhance the current clinical approach. Methods: Clinically relevant concentrations of VX2 carcinoma cells were suspended in artificial CSF. The neurapheresis system's ability to clear VX2 carcinoma cells was tested with and without the chemotherapeutic presence (methotrexate [MTX]). The VX2 cell concentration following each filtration cycle and the number of cycles required to reach the limit of detection were calculated. The ability of neurapheresis therapy to circulate, distribute, and maintain therapeutic levels of MTX was assessed using a cranial-spinal model of the SAS. The distribution of a 6 mg dose was monitored for 48 h. An MTX-specific ELISA measured drug concentration at ventricular, cervical, and lumbar sites in the model over time. Results: In vitro filtration of VX2 cancer cells with neurapheresis therapy alone resulted in a 2.3-log reduction in cancer cell concentration in 7.5 h and a 2.4-log reduction in live-cancer cell concentration in 7.5 h when used with MTX. Cranial-spinal model experiments demonstrated the ability of neurapheresis therapy to enhance the circulation of MTX in CSF along the neuraxis. Conclusion: Neurapheresis has the potential to act as an adjunct therapy for LM patients and significantly improve the standard of care. SN - 2632-2498 UR - https://www.unboundmedicine.com/medline/citation/32642705/Evaluation_of_neurapheresis_therapy_in_vitro:_a_novel_approach_for_the_treatment_of_leptomeningeal_metastases L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32642705/ DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.