Third Quarter 2016 - PowerPoint PPT Presentation

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*"%.='-"#(>-)4+34U3&#0#>D Web Exclusives > f!"#.#O+$O#(*31"O-.*1.#$$O7#+(1O'&,#O James Allison Says Rational Combinations Key to &).*$$O%"#O7*&.,O%"&%OQO%"+(4O5#O)&(O Immunotherapy Success in "Cold" Tumors $%&.%O%"+(4+(1O&7*3%O$*'#O*/O%"#O)*0,#.O Laura Panjwani @OncEditorLaura %3'*.$O.#$-*(,+(1O+/O5#O=3$%O !""#$ Published Online: Monday, Oct 31, 2016 %&'()*+,$-+($.-!*+,$/-&*0+-1$ Immunotherapy has been a game changer in oncology, 20.3*+-&*0+$("2*%*0+% 6gO$&+,OG00+$*(6O improving survival and providing long, durable responses in melanoma, lung, head and neck cancer, and others. -.*/#$$*.O&(,O)"&+.O*/OQ''3(*0*1<O&%O The success of immunotherapies in those cancers—which TKOG(,#.$*(OC&()#.OC#(%#.:O are likely seeing a better rate of response due to their high mutational burden—is now paving the way for what are known as “cold” tumors, those that don’t have a heavy fG$O5#O3(,#.$%&(,O%"+$O7#%%#.6O5#O)&(O mutational burden or significant T-cell infiltration, said James Allison, PhD. /-&*0+-11)$#'&$&40$&5*+,%$&0,"&5"/$ “There is enough progress being made across the board that &5-&$40+6&$7'%&$('#1*2-&"$0/$2-+2"1$ I think we can start thinking about some of the colder tumors "-25$0&5"/$0'& 6O73%O 4*11$(0$(*88"/"+&$ James Allison, PhD responding if we just keep studying and making rational combination decisions,” said Allison, professor and chair of &5*+,% %"&%O)&(O&%O0#&$%O7#O&,,+%+9#6O+/O Immunology at MD Anderson Cancer Center. “As we understand this better, we can rationally put two things together that won’t just duplicate or cancel each other out, but (*%O$<(#.1+$%+):gO will do different things that can at least be additive, if not synergistic.” *()0+9#:)*'6OLFO`)%ONHF_O Ne

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! ! V#3 V#3; V#3 E0+3+&.04E#/P+3.'+#34F.'. ! ! Combination Therapy with IL PV-10 and anti-CTLA-4 antibodies in B16-OVA bearing mice ! ! Treatment with anti-CTLA-4 antibodies in combination Treatment with anti-CTLA-4 antibodies in combination with IL with IL PV-10 results in smaller B16-OVA tumors PV-10 leads to the induction of B16-specific T cells 1600 70 Mean Tumor Weight (mg) 1400 IFN-gamma (pg/ml) 60 p=0.05 1200 50 ! ! 1000 40 800 B16 30 MC38 600 20 400 10 200 0 0 PBS PV10 anti-CTLA4 PV10+anti-CTLA4 PBS PV10 anti-CTLA4 PV10+anti-CTLA4 D81"3 U<"%2?($@(21W+( D81"3OU<"%2?($@(21W+(IJUP(,-)* \Z

V#3 V#3; V#3 E0+3+&.04E#/P+3.'+#34F.'. Combination Therapy with IL PV-10 and anti-PD-1 antibodies in B16-OVA bearing mice Treatment with anti-PD-1 antibodies in combination with IL Treatment with anti-PD-1 antibodies in combination with IL PV-10 results in reduced growth of B16-OVA tumor PV-10 leads to the induction of B16-OVA-specific T cells 80 3500 p<0.05 Mean Tumor Size (mm 2 ) 70 3000 ! ! IFN-gamma (pg/ml) 60 2500 PBS 50 PV10 2000 40 anti-PD1 30 1500 PV10+anti-PD1 ! ! 20 1000 10 p<0.05 500 0 0 5 10 15 20 25 0 PBS PV10 anti-PD1 PV10+anti-PD1 Days D81"3OU<"%2?($@(21W+(IJUP(,-)* ! ! \\ ! !

V#3 V#3; V#3 E0+3+&.04E#/P+3.'+#34F.'. Combination Therapy with IL PV-10 and anti-PD-L1 antibodies in B16 bearing mice Treatment with anti-PD-L1 antibodies in combination Treatment with anti-PD-L1 antibodies alone or in combination with IL PV-10 results in reduced growth of B16 tumor with PV-10 leads to the induction of B16-specific T cells 60 Mean Tumor size (mm 2 ) 2500 IFN-gamma (pg/ml) 50 2000 * * PBS + NrIgG 40 PBS + anti-PDL1 1500 30 PV10 + NrIgG 1000 PV10 + anti-PDL1 20 500 10 p<0.05 0 0 PBS PV10 anti-PDL1 PV10+anti-PDL1 0 5 10 15 20 25 *p<0.05 compared to PV-10 treated mice Days D81"3OU<"%2?($@(21W+(IJUP(,-)* IJUP(,-)* \_ ! ! ! ! ! ! ! !

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