GTB-3550 TriKE™ safely activates and delivers IL-15 to NK cells, but not T cells, in immune suppressed patients with advanced myeloid
malignancies, a novel paradigm exportable to solid tumors expressing HER2 or B7H3
GT BioPharma ◦ SAB, Research Support, Consulting, Stock options
Fate Therapeutics◦ Research Support, Consulting, Stock options
OnkImmune, Nektar◦ SAB
Vycellix◦ Consulting, Stock options
Disclosures
CD3/CD19-depletionOvernight IL-2 or IL-15
NK-enriched product
Cy 60 mg/kg x 2Flu 25 mg/m2 x 5
Relapsed/refractory AML
Surge IL-15
PBApheresis
1Miller et al, Blood, 2005; 2Bachanova et al, Blood 2014; 3Cooley et al, Blood Advances 2019
Allogenic NK Cell Adoptive Transfer:Two Decades and Hundreds of Patients
CD3/CD19-depletionOvernight IL-2 or IL-15
NK-enriched product
Cy 60 mg/kg x 2Flu 25 mg/m2 x 5
Relapsed/refractory AML
Surge IL-15
PBApheresis
1Miller et al, Blood, 2005; 2Bachanova et al, Blood 2014; 3Cooley et al, Blood Advances 2019
Allogenic NK Cell Adoptive Transfer:Two Decades and Hundreds of Patients
Lessons learned: More specificity is needed
TriKE
VHH
VH VL
αCD16
αCD33
IL-15
Efficient
Replacement Of scFv With Camelid VHH Single Domain Sequences
camTriKE better activates NK Cells but not T Cells
2nd Generation TriKE Function In Vivo
Click to edit Master title styleCam16/IL15/scFv HER2 TriKE Highly Effective Against Ovarian Cancer
Click to edit Master title stylecam1615camB7H3 TriKE Pan Solid Tumor Targeting
His tag
PE
B7H3+
Tumor
Percent CD107a+ NK Cells
Treatment Condition
Perc
ent N
K C
ells
NK only
NK+WT
NK+KO
NK WT 3n
M IL-15
NK KO 3nM IL
-15
NK WT 3n
M TriKe
NK KO 3nM TriK
E0
20
40
60
80
*
Percent IFN-gamma+ NK Cells
Treatment Condition
Perc
ent N
K C
ells
NK only
NK+WT
NK+KO
NK WT 3n
M IL-15
NK KO 3nM IL
-15
NK WT 3n
M TriKe
NK KO 3nM TriK
E0
10
20
30
40*
IncuCyte-based killing assay. 20,000OVCAR8-GFP cells were allowed toform a spheroid over 3 days, and then40,000 NK were added alone or withB7H3 TriKE.
cam camIL15
Team ScienceUniversity of Minnesota
LaboratoryMartin FelicesDaniel ValleraFrank CichockiNick ZorkoBruce WalcheckAimee MerinoBin ZhangTodd LenvikZachary DavisPippa KennedyUpasana ArvindaEmily ChiuJake Myers
GMP FacilityDavid McKenna, MDDarin SumstadDiane KadidloWilliam SharkeyAndy Sicheneder
Faculty/MDsMark JuckettDaniel J WeisdorfJohn WagnerBruce BlazarClaudio BrunsteinVeronika BachanovaMelissa GellerJoseph Maakaron
