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An immunoadhesin therapy for glioblastoma targeting CD97

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43CA233386-01
Agency Tracking Number: R43CA233386
Amount: $263,999.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA17-302
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-07-04
Award End Date (Contract End Date): 2019-06-30
Small Business Information
25571 CLAWITER RD
Hayward, CA 94545-2740
United States
DUNS: 052917593
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 KEITH WYCOFF
 (650) 857-1332
 kwycoff@planetbiotechnology.com
Business Contact
 ELLIOTT FINEMAN
Phone: (510) 887-1461
Email: efineman@planetbiotechnology.com
Research Institution
N/A
Abstract

Effective treatment of glioblastomaGBMthe most common and most lethal human brain tumorrepresents one of the most formidable challenges in oncologyDespite the use of surgeryradiation therapy and
chemotherapythe prognosis for patients with GBM remains poorIt is the infiltrative nature of these tumors
that eliminates the possibility of curative surgical resectionConventional DNA damaging chemotherapies may
exhibit limited duration of efficacy because GBM cells are proficient at repairing DNA damageleading to drug
resistanceCDis a cell surface protein that is significantly upregulated in GBM and overexpression confers
an invasive phenotype to glioblastoma cells and is associated with decreased survival of GBM patientsBecause
of thisCDis an attractive therapeutic target for GBMThe extracellular region of CDcontains binding
sites for a number of cellular ligandsone of which is CDthe decay accelerating factor for complementalso
known as DAFWe have produced fusions of human DAF with human IgGFc and have demonstrated a strong
neutralizing interaction between DAF Fc and CDwith resulting inhibition of GBM migration in culture and
a profound antibody dependent cellular cytotoxicityADCCreaction against GBM cellsWe therefore propose
developing DAF Fc as a GBM therapyWe will produceusing our plant expression systemadditional forms of DAF Fcmodified to have
improved ADCC activity and be retained more efficiently in the brainWe will evaluate the ability of these DAFFc variants to bind to purified CDand CDexpressing GBM cellsand to kill GBM cells in ADCC assaysWe
will also compare the ability of the DAF Fc variants to inhibit GBM cell migrationproliferationcomplement
activationand angiogenesisWe will compare the in vivo activity of DAF Fc variants against patient derived
human glioblastoma intracranial xenografts in immunodeficient miceas well as verify the lack of toxicity of
DAF Fc treatmentWe anticipate that these studies will validate our hypothesis regarding the impact of CDon GBM biology and will eventually impact the poor prognosis faced by patients with this devastating cancer Effective treatment of glioblastomaGBMthe most common and most lethal human
brain tumorrepresents one of the most formidable challenges in oncologyCDa cellsurface protein that is significantly upregulated in GBM is an attractive therapeutic targetBased on strong preliminary data showing that decay accelerating factorDAFfused to
IgG Fc binds to CDon GBM cellsinhibits tumor growthmigration and invasivenessand promotes ADCCwe propose developing DAF Fc as a GBM therapy

* Information listed above is at the time of submission. *

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