*Glioblastomas &Immunotherapy

Created by: Lystia Villanueva

*What is a Glioblastoma

(GBM) ?* Also known as glioblastoma multiforme

* Brain tumor that arises from normal brain cells

* Most common brain tumor and highly malignant astrocytoma,

* Usually grade IV tumor

* Represents about 15% of all brain tumors (Source: Neurosurgery UCLA, n.d.)

*What is a Glioblastoma

(GBM) ?* Frequently seen in more men > women

* Occurs most often 50–75 years

* Tumor found in very vascularized areas of brain, easily

infiltrates surrounding areas

* Dismal prognosis of ~ 14 months (Source: Neurosurgery UCLA, n.d.)

*Diagnosis* Physical Exam* Radiological tests*MRIs*CT Scans

* Surgical Biopsy (Source: Neurosurgery UCLA, n.d.)

(Source: Brain Anatomy and Images, n.d.) (Source: American Journal of Neuroradiology, n.d.)

(Source: Geneva Foundation for Medical Education and Research, 2014)

MRI Images of Patients with Glioblastomas

*Symptoms* Headaches

* Seizures

* Convulsions

* Impaired vision

* Speech problems

* Weakness and numbness in certain body areas

* Cognitive problems (Source: Neurosurgery UCLA, n.d.)

* Treatments

Surgical excision of GBM.

(Source: Nuborfacureslides, 2009)

*Chemotherapy*Radiation*Open surgery*Stereotactic Surgery*Chemo wafers placed on brain

(Source: Neurosurgery UCLA, n.d.)

(Source: Geneva Foundation for Medical Education and Research, 2014)

Scalp Metastasis from Glioblastoma

High Power Microscopic Images of GBM

(Source: Frontier in Bioscience, n.d.)

*Gene Mutations in Glioblastomas

(Source: USParmacist, 2010)

*Treatments*Multiple genetic mutations in GBMs

*Blood-Brain barrier = inaccessible to most cytotoxic medications

*Prognosis is still poor with current modes of treatment(Source: Journal of Neuro-Oncology, 2015)

*New and Active Area of Research

*IMMUNOTHERAPY-Generation of immune response to GBMs *Create a personalized vaccine- DCVax-L*Use of patient’s dendritic cells-special immune system cells

(Source: Solutions for Injections, n.d.)

(Source: Journal of Neuro-Oncology, 2015)

*New and Active Area of Research

*Now in clinical phase III

*Target rapid proliferating malignant cells

*Destruction of GBM (Source: Journal of Neuro-Oncology, 2015)

(Source: Northwest Biotherapeutics, n.d.)

*Mobilization of Immune System

*Patient’s GBM tumor tissue surgically excised*Antigens from Tumor tissue obtained from patient

*Patient’s Blood drawn to obtain immune cells (leukapheresis) *Dendritic cells obtained from sample *loaded with patient’s antigens(education of dendritic cells)*In-vitro maturation of Dendritic cells,

*Creation of DCVax-L vaccine from highly purified ‘activated & educated dendritic cells’

(Source: Northwest Biotherapeutics, n.d.)

*Mobilization of Immune System

*Personalized vaccine created*Intradermal*Given every 2 weeks, for 6 weeks; booster shots every 3 months

*Dendritic cells in vaccine signals other immune cells - T cells, B cells*Specific tumor cells located and attacked by immune cells that have not been immunosuppressed(Source: Northwest Biotherapeutics, n.d.)

(Source: Northwest Biotherapeutics, n.d.)

*Dendritic Cells in Action

(Source: Journal of Neuro-Oncology, 2015)

*GBM Survivor*DCVax-L has delayed tumor growth & prolonged lives - Great potential!*33% of trial I/II phase patients lived >4 yrs.*27% lived more than 6 yrs.*2 have survived ~ 10 yrs.*The following is a YouTube with survivor’s

storyhttps://youtu.be/Wki-goEEYnY

(Source: Northwest Biotherapeutics, n.d.)

*References*Antonios, J. P., Everson, R. G., & Liau, L. M. (2015). Dendritic cell

immunotherapy for brain tumors. Journal of Neuro-Oncology. Retrieved from http://link.springer.com/10.1007/s11060-015-1830-1

*Brain Anatomy and Images Gross. (n.d.). Retrieved from http://www.aboutcancer.com/brain_anatomy_abnormal.htm

*Brown, G. L., Eckley, M., & Wargo, K. A. (2010, May 20). USPharmacist.com > A Review of Glioblastoma Multiforme. Retrieved from http://www.uspharmacist.com/content/s/125/c/20820/

*Ellor, S. V., Pagano-Young, T. A., & Avgeropoulos, N. G. (2014). Glioblastoma: Background, Standard Treatment Paradigms, and Supportive Care Considerations. Journal Of Law, Medicine & Ethics, 42(2), 171-182. doi:10.1111/jlme.12133

*Ferroli, P., Schiariti, M., Finocchiaro, G., Salmaggi, A., Castiglione, M., Acerbi, F., & ... Broggi, G. (2013). Operability of glioblastomas: "sins of action" versus "sins of non-action". Neurological Sciences, 34(12), 2107-2116. doi:10.1007/s10072-013-1345-5

*Finocchiaro, G., & Pellegatta, S. (2014). Perspectives for immunotherapy in glioblastoma treatment. Current Opinion In Oncology, 26(6), 608-614. doi:10.1097/CCO.0000000000000135

*References*Frontiers in Bioscience: A virtual library of medicine. (n.d.). Retrieved

from https://www.bioscience.org/search-article/index.php?keywords=glioblastoma+&author_names=&year=&volume=&pages=&pubmed_no=&abstract=&submit=1

*Northwest Biotherapeutics Dendritic Cell Immunotherapy - Northwest Biotherapeutics. (n.d.). Retrieved from http://www.nwbio.com/dendritic-cell-immunotherapy/

*nuborfacureslides: Março 2009. (2009, March). Retrieved from http://nuborfacureslides.blogspot.com/2009_03_01_archive.html

*Selected medical images. (2014). Retrieved from http://www.gfmer.ch/selected_images_v2/detail_list.php?offset=30&cat1=3&cat3=96&stype=d

*Solution for injections photo. Image № 18974. (n.d.). Retrieved from http://www.torange.us/Objects/medicine/Solution-for-injections-18974.html

*UCLA Neurosurgery Brain Tumor Nanotechnology Laboratory. (n.d.). Retrieved from http://neurosurgery.ucla.edu/body.cfm?id=1273