Induction and analysis of antigen-specific T cell responses in
melanoma patients and animal model
Bins, A.D.
Citation
Bins, A. D. (2007, March 15). Induction and analysis of antigen-specific T cell responses in
melanoma patients and animal model. Retrieved from https://hdl.handle.net/1887/11457
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the
Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/11457
Note: To cite this publication please use the final published version (if applicable).
2QWKH5ROHRI0HODQRPD6SHFLILF&'
7&HOO
,PPXQLW\LQ'LVHDVH3URJUHVVLRQRI$GYDQFHG
6WDJH0HODQRPD3DWLHQWV
$GULDDQ %LQV 0RQLTXH YDQ 2LMHQ 6MRHUG (OLDV -RKDQ 6HLQ 3DXOLQH
:HGHU *LMVEHUW GH *DVW +HQN 0DOOR 0DDUWHQ *DOOHH +DUP YDQ
7LQWHUHQ7RQ6FKXPDFKHUDQG-RKQ+DDQHQ
'LYLVLRQV RI ,PPXQRORJ\ 0HGLFDO 2QFRORJ\ 2QFRORJLF 'LDJQRVWLFV DQG 6WDWLVWLFV7KH1HWKHUODQGV&DQFHU,QVWLWXWH$PVWHUGDPWKH1HWKHUODQGV
$EVWUDFW
&\WRWR[LF7FHOO LPPXQLW\ GLUHFWHG DJDLQVW PHODQRVRPDO GLIIHUHQWLDWLRQDQWLJHQV
LV DUJXDEO\ WKH EHVWVWXGLHG DQG PRVW SUHYDOHQW IRUPRI WXPRUVSHFLILF 7FHOO
LPPXQLW\ LQ KXPDQV 'HVSLWH WKLV WKHUROH RI 7FHOO UHVSRQVHV GLUHFWHG DJDLQVW
PHODQRVRPDODQWLJHQVLQGLVHDVHSURJUHVVLRQKDVQRWEHHQHOXFLGDWHG7RDGGUHVV
WKLVLVVXH ZH KDYH UHODWHG WKH SUHVHQFH RI FLUFXODWLQJ PHODQRPDVSHFLILF7
FHOOV ZLWK GLVHDVH SURJUHVVLRQ DQG VXUYLYDO LQ D ODUJH FRKRUWRI SDWLHQWV ZLWK
DGYDQFHGVWDJHPHODQRPDZKRKDGQRWUHFHLYHGSULRUWUHDWPHQW,QRI
SDWLHQWV PHODQRPDVSHFLILF7 FHOOV ZHUH GHWHFWHG VRPHWLPHV LQ VXUSULVLQJO\
ODUJHQXPEHUV'LVHDVHSURJUHVVLRQGXULQJWUHDWPHQWZDVPRUHIUHTXHQWLQSDWLHQWV ZLWK FLUFXODWLQJ PHODQRPDVSHFLILF 7 FHOOV DQG PHDQ VXUYLYDORI SDWLHQWV ZLWK
FLUFXODWLQJPHODQRPDVSHFLILF7FHOOVZDVHTXDOWRWKHVXUYLYDORISDWLHQWVZLWKRXW
PHODQRPDVSHFLILF7FHOOV7KHVHGDWDVXJJHVWWKDWWKHLQGXFWLRQRIPHODQRVRPDO
GLIIHUHQWLDWLRQDQWLJHQVSHFLILF7FHOOUHDFWLYLW\LQDGYDQFHGVWDJHPHODQRPDLVD
ODWHHYHQWPRVWOLNHO\GXHWRDQWLJHQORDGDQGVSUHDGLQJDQGLVQRWDFFRPSDQLHG
E\DFOLQLFDOO\VLJQLILFDQWDQWLWXPRUHIIHFW7KHVHPHODQRPDVSHFLILF7FHOOVPD\
EHIXQFWLRQDOO\GLVWLQFWIURP7FHOOVUDLVHGGXULQJVSRQWDQHRXVUHJUHVVLRQRUXSRQ
YDFFLQDWLRQ
,QWURGXFWLRQ
0HODQRPD LV FRQVLGHUHG RQH RI WKH PRVW LPPXQRJHQLF WXPRUV 6SRQWDQHRXV UHPLVVLRQV RFFDVLRQDOO\ RFFXU LQ PHODQRPD SDWLHQWV DOEHLW LQIUHTXHQWO\ DQG LPPXQRWKHUDS\LQGXFHG UHPLVVLRQV FRUUHODWH ZLWK DXWRLPPXQH VNLQ
GHSLJPHQWDWLRQ 7KHVH SKHQRPHQD KDYH DWOHDVW LQ SDUW EHHQ DWWULEXWHG
WR D FHOOXODU LPPXQH UHVSRQVHEHFDXVH WKH SUHVHQFH RI WXPRULQILOWUDWLQJ 7
O\PSKRF\WHVLQSULPDU\PHODQRPDDQGLQPHODQRPDO\PSKQRGHPHWDVWDVHVDUH
LQGHSHQGHQWSRVLWLYHSURJQRVWLFIDFWRUV
,QSDVW\HDUVH[WHQVLYHHIIRUWVWRLGHQWLI\WDUJHWPROHFXOHVIRUPHODQRPDUHDFWLYH
7 FHOOV KDYH UHVXOWHG LQ WKH LGHQWLILFDWLRQRI D ODUJH VHW RI PHODQRPDDVVRFLDWHG
DQWLJHQV7KHVHDQWLJHQVFDQEHFODVVLILHGDVPHODQRF\WHOLQHDJHVSHFLILFDQWLJHQV
0$570HODQ$W\URVLQDVHJSDQGDQWLJHQVGHULYHGIURPJHQHVH[SUHVVHG LQWHVWLVDQGDYDULHW\RIFDQFHUVLQFOXGLQJ0$*(IDPLO\1<(6235$0(
0HODQRF\WHOLQHDJHDQWLJHQVDUHH[SUHVVHGLQDODUJHIUDFWLRQRIPHODQRPDVDQGD
VXEVWDQWLDOQXPEHURIHSLWRSHVIURPWKHVHDQWLJHQVWKDWDUHUHFRJQL]HGE\F\WRWR[LF
7FHOOVKDYHEHHQPDSSHG:LWKWKHDLGRIVROXEOHWHWUDPHUL]HG0+&FRPSOH[HV
FRQWDLQLQJWKHVHHSLWRSHVPHODQRVRPDODQWLJHQVSHFLILF&'7FHOOVKDYHEHHQ
GHWHFWHGLQSHULSKHUDOEORRGIURPPHODQRPDSDWLHQWV/DUJHH[SDQVLRQVRIWKHVH
7FHOOVDUHSULPDULO\REVHUYHGLQWKHSHULSKHUDOEORRGRUWXPRULQILOWUDWHGO\PSK QRGHVIURPVWDJH,,,DQGSDUWLFXODUO\VWDJH,9PHODQRPDSDWLHQWV,QSDWLHQWVZLWK
WXPRUVWKDWDUHFRQILQHGWRWKHSULPDU\VLWHVXFKDVLQVWDJH,DQG,,PHODQRPD0+&
WHWUDPHUSRVLWLYH7FHOOVKDYHEHHQIRXQGEXWDWVLJQLILFDQWO\ORZHUIUHTXHQFLHV
'HVSLWHWKHSUHVHQFHRIQDWXUDOO\RFFXUULQJPHODQRPDVSHFLILF7FHOOLPPXQLW\
LQDODUJHSURSRUWLRQRIPHODQRPDSDWLHQWVVSRQWDQHRXVUHPLVVLRQVLQWKLVJURXS
RISDWLHQWVDUHH[WUHPHO\UDUHDQGLWLVFXUUHQWO\XQFOHDUZKDWWKHVLJQLILFDQFHLVRI VSRQWDQHRXVPHODQRPDVSHFLILF7FHOOLPPXQLW\IRUWKHVHSDWLHQWV
3DWLHQWV 0HWKRGV 3DWLHQWV
3HULSKHUDO EORRG VDPSOHV ZHUH WDNHQ IURP +/$$ DGYDQFHGVWDJH PHODQRPD SDWLHQWV VWDJH ,9 DW WKH WLPH WKDW WKH\ KDG EHHQGLDJQRVHG ZLWK
PHWDVWDWLF PHODQRPD 1RQH RI WKH SDWLHQWV KDGXQGHUJRQH SULRU WUHDWPHQW IRU
PHWDVWDWLF PHODQRPD 3DWLHQWVZHUH WUHDWHG ZLWK VWDQGDUG FKHPRWKHUDS\ ZLWK RU
ZLWKRXWF\WRNLQHWKHUDS\PRVWO\DVSDUWRIDFOLQLFDOWULDODVLQGLFDWHGLQ7DEOH
0+&7HWUDPHUV
0+&FODVV,WHWUDPHULFFRPSOH[HVZHUHSUHSDUHGDVSUHYLRXVO\GHVFULEHGZLWKPLQRU
PRGLILFDWLRQV+/$$SHSWLGHFRPSOH[HVZHUHJHQHUDWHGZLWKWKHIROORZLQJ
ILYH DQWLJHQLF SHSWLGHV DLQIOXHQ]D$ PDWUL[± E *,/*)9)7/ 0$57
±F (/$*,*,/79 $/ YDULDQW G W\URVLQDVH±<0'*70649
1' YDULDQW DQG H JS±</(3*397 $9 YDULDQW 0+&
FODVV ,SHSWLGH FRPSOH[HVZHUH VXEVHTXHQWO\ SXULILHG ELRWLQ\ODWHG E\ ELRWLQ
OLJDVHSXULILHGDQGFRQYHUWHGWRWHWUDPHUVE\WKHDGGLWLRQRISK\FRHU\WKULQODEHOHG VWUHSWDYLGLQ0ROHFXODU3UREHVDQGVWRUHGDW±&LQJO\FHURO%6$
0+&7HWUDPHU6WDLQLQJ
,WKDVSUHYLRXVO\EHHQVKRZQWKDW&'FDQSOD\DFULWLFDOUROHLQWKHELQGLQJRI
0+&WHWUDPHUVWRDQWLJHQVSHFLILF7FHOOV,QSDUWLFXODULQFDVHRIORZ
DIILQLW\7FHOOUHFHSWRUVWKHVLPXOWDQHRXVELQGLQJRI&'WRWKH0+&ĮGRPDLQ LVQHFHVVDU\WRREWDLQDVXIILFLHQWO\VWDEOHFRPSOH[EHWZHHQ0+&WHWUDPHUVDQG
DQWLJHQVSHFLILF7FHOOVDQGLQVXFKFDVHVFRVWDLQLQJZLWK&'FDQEORFN0+&
WHWUDPHUELQGLQJ,QOLQHZLWKWKLVZHREVHUYHGGLPLQLVKHG0+&WHWUDPHU VWDLQLQJRIDW\URVLQDVHVSHFLILF7FHOOFORQHLQWKHSUHVHQFHRI&'PRQRFORQDO
DQWLERG\/LNHZLVHDODUJHIUDFWLRQRIWKHW\URVLQDVHVSHFLILF&'7FHOOVLQWKH
SHULSKHUDO EORRG RIDGYDQFHGVWDJH PHODQRPD SDWLHQWV EHFDPH XQGHWHFWDEOH E\
0+&WHWUDPHU VWDLQLQJ LQ WKH SUHVHQFH RI &' PRQRFORQDO DQWLERG\GDWD QRW
VKRZQ 7R RYHUFRPH WKLV LVVXH SHULSKHUDO EORRG PRQRQXFOHDUFHOOV 3%0&V ZHUH VWDLQHG ZLWK D VHW RI OLQHDJH OLQ PDUNHUDQWLERGLHV VSHFLILF IRU %FHOOV
&'QDWXUDONLOOHUFHOOV&'PRQRF\WHV&'JUDQXORF\WHV&'DQG
&' 7 FHOOV&' DQG WKH OLQQHJDWLYH O\PSKRF\WH VXEVHW ZDV XVHG IRU DQDO\VLV
/LQQHJDWLYHO\PSKRF\WHVDUH!&'SRVLWLYHDQG+/$$W\URVLQDVHWHWUDPHU
SRVLWLYH FHOOV ZLWKLQ WKH OLQQHJDWLYH SRSXODWLRQ DUHOLNHZLVH ! &'SRVLWLYH
WKHUHE\YDOLGDWLQJWKLVVWUDWHJ\)LJ
7KDZHG 3%0& VDPSOHV ZHUH LQFXEDWHG RYHUQLJKW DW & LQ,VFRYH¶ V PHGLXP
ZLWK)&6WRUHFRYHU3%0&VDQGHOLPLQDWHDSRSWRWLFFHOOV$IWHUZDVKLQJ
WKHFHOOVZHUHLQFXEDWHGIRUPLQLQFROG3%6 ZLWK%6$DQGQRUPDO
PRXVHVHUXPWREORFN)FUHFHSWRUV7ZRPLOOLRQFHOOVSHUVDPSOHZHUHLQFXEDWHG IRUPLQZLWKJPOSK\FRHU\WKULQODEHOHG0+&WHWUDPHUDW&&'7
FHOOVZHUHQHJDWLYHO\VHOHFWHGE\VWDLQLQJZLWKDODUJHVHWRI),7&ODEHOHGOLQHDJH
PDUNHU DQWLERGLHV&' &' &' &' &' %HFWRQ'LFNLQVRQ &HOOV
ZHUHVWDLQHGZLWKSURSLGLXPLRGLGHWREHDEOHWRJDWHRXWGHDGFHOOV6DPSOHVZHUH
DQDO\]HGE\IORZF\WRPHWU\XVLQJD)$&6FDOLEXUDQG&HOO4XHVWVRIWZDUH%HFWRQ
'LFNLQVRQ)RUZDUGDQGVLGHVFDWWHUSDUDPHWHUVZHUHXVHGWRGHILQHO\PSKRF\WH
SRSXODWLRQV
%DFNJURXQGDQGGHWHFWLRQOLPLWVZHUHVHSDUDWHO\HVWDEOLVKHGIRUHDFKWHWUDPHUE\
VWDLQLQJRI3%0&VIURPIRXU+/$$QHJDWLYHLQGLYLGXDOVZLWKSK\FRHU\WKULQ
ODEHOHG 0+&WHWUDPHUV DQG WKHSDQHO RI ),7&ODEHOHG DQWLERGLHV ,I PRUH WKDQ
&'&'FHOOV FRXOG EH DQDO\]HG E\ IORZ F\WRPHWU\ LQ WKH +/$$
SRVLWLYHVDPSOHVWKHPHDQSHUFHQWDJHRI0+&WHWUDPHUSRVLWLYHFHOOV[6'RI
IRXU+/$$QHJDWLYH3%0&VDPSOHVZDVXVHGDVWKHGHWHFWLRQOLPLWIRUSRVLWLYH
0+&WHWUDPHUVWDLQLQJ,IOHVVWKDQ&'&'FHOOVFRXOGEHDQDO\]HGWKH
PHDQSHUFHQWDJH[6'ZDVXVHGDVWKHGHWHFWLRQOLPLW
,PPXQRKLVWRFKHPLVWU\
)RUPDOLQIL[HG SDUDIILQHPEHGGHG PDWHULDO RI PHODQRPD PHWDVWDVHV ZDV
DYDLODEOH IURP RI SDWLHQWV 6HFWLRQV PZHUH VWDLQHG IRU 0$57
$E 1HRPDUNHUV W\URVLQDVHFORQH7 1HRPDUNHUV JS
+0%'$.2RU+/$$+&$JHQHURXVO\GRQDWHGE\-1HHIMHV
1HWKHUODQGV&DQFHU ,QVWLWXWH $PVWHUGDP )RU DOO VWDLQLQJV H[FHSWIRU
JSOPLFURZDYHDQWLJHQUHWULHYDOLQFLWUDWHEXIIHUZDVSHUIRUPHG6WDLQLQJVZHUH
SHUIRUPHGZLWKVWDQGDUGDONDOLQHSKRVSKDWDVHWKUHHVWHSLPPXQRKLVWRFKHPLVWU\ 6WDWLVWLFV
(QG SRLQW RI WKH VWXG\ ZDV RYHUDOO VXUYLYDO PHDVXUHG IURP VWDUWRI WUHDWPHQW
XQWLOGHDWKRUODVWIROORZXS3DWLHQWVDOLYHDWWKHWLPHRIDQDO\VHVZHUHFHQVRUHG
6XUYLYDO HVWLPDWHV DQG FXUYHVZHUH PDGH ZLWK WKH .DSODQ0HLHU WHFKQLTXH DQG
GLIIHUHQFHV EHWZHHQJURXSV ZHUH WHVWHG E\ D ORJUDQN WHVW &R[ SURSRUWLRQDO
KD]DUGDQDO\VLVZDVXVHGWRHVWLPDWHWKHVL]HRIWKHHIIHFWKD]DUGUDWLRZLWK
FRQILGHQFHLQWHUYDOV7KHUHODWLRQRI0$57ZLWKUHVSRQVHLQWKUHHFDWHJRULHV ZDVWHVWHGE\D&RFKUDQH$UPLWDJHWUHQGWHVW:LOFR[RQWHVWZDVXVHGWRSHUIRUP
DVWDWLVWLFDODQDO\VLVRQWKHSKHQRW\SLFDOFKDUDFWHULVWLFVWKDWGLVWLQJXLVKQDwYHDQG
HIIHFWRUPHPRU\0$57VSHFLILF7FHOOV 5HVXOWV
3DWLHQWV
%HWZHHQDQG+/$$ SRVLWLYHSDWLHQWVZHUHHQUROOHG7DEOH
$OO SDWLHQWV KDG DGYDQFHGVWDJH PHODQRPDVWDJH ,9 ZLWK D PHGLDQ RUJDQ
LQYROYHPHQWRIUDQJH±7KHPDMRULW\RIRIWKHSDWLHQWVKDGYLVFHUDO
PHWDVWDVHVPRVWO\ LQ OXQJ DQGRU OLYHU 1RQYLVFHUDO PHWDVWDVHV RI ZHUH
PRVWRIWHQORFDWHGLQO\PSKQRGHVDQGVXEFXWLV)LYHSDWLHQWVZHUHWUHDWHGZLWK
VWDQGDUGGDFDUED]LQHPJPHYHU\ZHHNVSDWLHQWVZHUHWUHDWHGZLWK
WHPR]RORPLGHPJPIRUGD\VHYHU\ZHHNVDQGSDWLHQWVZHUHWUHDWHG
ZLWK FRPELQHGFKHPRELRWKHUDS\ WHPR]RORPLGH IRU GD\V WULSOH F\WRNLQH
LQWHUOHXNLQLQWHUIHURQĮJUDQXORF\WHPDFURSKDJHFRORQ\VWLPXODWLQJIDFWRUIRU
GD\VHYHU\ZHHNV7KHODWWHUWZRWUHDWPHQWVZHUHJLYHQDVSDUWRI3KDVH,,
DQG,,,FOLQLFDOWULDOV
$QDO\VLVRI3DWLHQW'HULYHG3HULSKHUDO%ORRG6DPSOHV
3HULSKHUDO EORRG VDPSOHV ZHUH REWDLQHG EHIRUH LQLWLDWLRQ RIWKHUDS\ DQG ZHUH
DQDO\]HG IRU WKH SUHVHQFH RI PHODQRPDVSHFLILF&' 7 FHOOV )LJ ,Q
SDWLHQWV 0$57VSHFLILF&' 7 FHOOV ZHUH GHWHFWDEOH DQG SDWLHQWV
GLVSOD\HGH[SDQVLRQV RI W\URVLQDVHVSHFLILF &' 7 FHOOV (LJKW RI WKHVH ODWWHU SDWLHQWV DOVR KDG 0$57VSHFLILF 7 FHOOV 2QO\ SDWLHQWWHVWHG SRVLWLYH
IRUJSVSHFLILF&'7FHOOVWKLVSDWLHQWDOVRKDGKLJKQXPEHUVRIFLUFXODWLQJ
0$57VSHFLILF7FHOOVRIWRWDO&'7FHOOSRRO,QWKHYDVWPDMRULW\RI
VDPSOHVWKDWFRQWDLQHGW\URVLQDVHVSHFLILF7FHOOVWKHVH&'7FHOOVZHUHFOHDUO\
GHWHFWDEOHZKHQFRXQWHUVWDLQHGXVLQJWKHSDQHORIOLQHDJHPDUNHUDQWLERGLHVEXW
ZHUHGLIILFXOWWRGHWHFWZKHQFRVWDLQLQJZLWKDQWL&'DQWLERG\ZDVSHUIRUPHG,Q
OLQHZLWKWKLVWKHDYLGLW\RIW\URVLQDVHVSHFLILF7FHOOVDSSHDUVORZHUWKDQWKDWRI
0$57RUJSVSHFLILF7FHOOVDVMXGJHGIURPWKHLQWHQVLW\RI0+&WHWUDPHU
VWDLQLQJ$VDFRQWUROLQIOXHQ]D$YLUXVVSHFLILF&'7FHOOVFRXOGEHGHWHFWHGLQ
RISDWLHQWVDQDO\]HGQ ,QWKHPDMRULW\RISDWLHQWV>RI@ZLWK
0+&WHWUDPHU7FHOOVWKHIUHTXHQFLHVRIPHODQRPDVSHFLILF7FHOOVLQSHULSKHUDO
EORRGZHUHDERYH&'7FHOOVUDQJLQJIURPWR
0$57VSHFLILF&'7FHOOVKDYHEHHQGHWHFWHGLQWKHSHULSKHUDOEORRGRIKHDOWK\
LQGLYLGXDOVLQIUHTXHQFLHVXSWRRI'DWDIURP'XWRLWHWDOLQGLFDWH
WKDWWKHVHSRSXODWLRQVDUHDGLUHFWUHIOHFWLRQRIDKLJKWK\PLFRXWSXWRI7FHOOVZLWK WKLVVSHFLILFLW\DQGLQOLQHZLWKWKLVWKHVH0$57VSHFLILF7FHOOVGLVSOD\DQDwYH
SKHQRW\SH7RHVWDEOLVKZKHWKHUWKH0$57VSHFLILF7FHOOSRSXODWLRQVGHWHFWHG
LQRXUFRKRUWDURVHWKURXJKDQWLJHQGULYHQH[SDQVLRQWKH0+&WHWUDPHUSRVLWLYH
&' 7 FHOO VXEVHW ZDV DQDO\]HG GLUHFWO\ H[ YLYR IRU FHOO VXUIDFHH[SUHVVLRQ RI
QDwYHHIIHFWRUDQGPHPRU\W\SHDVVRFLDWHGPDUNHUV,QKXPDQVWKH&'5$
DQG &'52 VXUIDFH DQWLJHQV KDYHEHHQ XVHG WR LGHQWLI\ QDwYH DQG PHPRU\ 7
FHOOVUHVSHFWLYHO\DQGFRVWDLQLQJIRU&'H[SUHVVLRQPD\EHXVHGWRGLVWLQJXLVK EHWZHHQHIIHFWRUFHOOVDQGQDwYHRUPHPRU\7FHOOV8VLQJWKH:LOFR[RQWHVW
ZH IRXQG WZR VWDWLVWLFDOO\ GLVWLQFWSDWWHUQV RI FHOO VXUIDFH H[SUHVVLRQ 7DEOH
,Q SDWLHQWVZLWK ORZ EXW GHWHFWDEOH IUHTXHQFLHV RI 0$57VSHFLILF7
FHOOV H[SUHVVLRQ RI &'5$ DQG &' ZHUH KLJK 3 DQG 3
UHVSHFWLYHO\DQGH[SUHVVLRQRI&'52ZDVORZ3 7KLVSDWWHUQRI
FHOOVXUIDFHH[SUHVVLRQUHIOHFWVDQDwYHSKHQRW\SH,QFRQWUDVWLQSDWLHQWVZLWKKLJK
IUHTXHQFLHV! RI 0$57VSHFLILF 7 FHOOV &'52 H[SUHVVLRQ ZDVKLJK
ZKHUHDVH[SUHVVLRQRI&'5$DQG&'ZDVRIWHQUHGXFHGDVFRPSDUHGZLWK
QDwYH7FHOOV,QSDWLHQWVZLWK±0$57VSHFLILF7FHOOVERWKQDwYHDQG
DQWLJHQH[SHULHQFHGSKHQRW\SHVZHUHIRXQG
,QVXPPDU\LQOLQHZLWKSULRUGDWDWZRJURXSVRISDWLHQWVFDQEHGLVWLQJXLVKHG
RQHJURXS>RIZLWKORZQXPEHUVRI0$57VSHFLILF&'7FHOOV
LQ SHULSKHUDO EORRG DQG D VHFRQGJURXS > RI @ ZLWK KLJK QXPEHUV
RI 0$57VSHFLILF7 FHOOV 7KH SKHQRW\SH RI WKH 0$57VSHFLILF 7 FHOOV RI
WKHPDMRULW\ RI WKHVH SDWLHQWV KDV EHHQ DQDO\]HG WKH DQDO\VLV FRQILUPVWKDW LQ
SDWLHQWVZLWKORZQXPEHUVRI0$57VSHFLILF7FHOOVWKHVHFHOOVGLVSOD\DQDwYH
SKHQRW\SHZKHUHDVWKRVHFHOOVLQSDWLHQWVKDYLQJKLJKQXPEHUVDUHSKHQRW\SLFDOO\
DQWLJHQH[SHULHQFHG
0HODQRPD6SHFLILF7FHOOVDQG6XUYLYDO
$OWKRXJK WKH SUHVHQFH RI PHODQRF\WH GLIIHUHQWLDWLRQ DQWLJHQVSHFLILF7 FHOO
LPPXQLW\ LQ SDWLHQWV ZLWK VWDJH ,9 GLVHDVH LV ZHOO GRFXPHQWHGWKH UHOHYDQFH
RI WKHVH 7FHOO UHVSRQVHV LQ WHUPV RI UHVSRQVHWR WUHDWPHQW RU VXUYLYDO UHPDLQ
XQNQRZQ:HWKHUHIRUHDWWHPSWHGWRUHODWHWKHSUHVHQFHRIPHODQRPDVSHFLILF7
FHOOVWRVXUYLYDOLQWKLVODUJHFRKRUWRI+/$$ VWDJH,9PHODQRPDSDWLHQWV 0HGLDQ IROORZXS ZDV PRQWKV$W WKH WLPH RI DQDO\VLV SDWLHQWV KDG GLHG
DQGWKHPHGLDQVXUYLYDORIDOOSDWLHQWVZDVPRQWKV)LJFRQILGHQFH
LQWHUYDO ±PRQWKV 7KLV LV LQ FORVH DJUHHPHQW ZLWK WKH PHGLDQ VXUYLYDO REVHUYHGLQVHYHUDOUDQGRPL]HGFOLQLFDOWULDOVXVLQJGLPHWK\OWULD]HQRLPLGD]ROH
FDUER[DPLGHRU WHPR]RORPLGHEDVHG WUHDWPHQW UHJLPHQV IRU DGYDQFHGVWDJH PHODQRPDSDWLHQWV
7RWHVWZKHWKHUWKHSUHVHQFHRIFLUFXODWLQJPHODQRPDVSHFLILF&'7FHOOVZDV
UHODWHG WR FOLQLFDO RXWFRPH VXUYLYDO RI SDWLHQWVWKDW KDG GHWHFWDEOH QXPEHUV RI
FLUFXODWLQJ PHODQRPDVSHFLILF7 FHOOV ZDV FRPSDUHG ZLWK WKRVH ZLWKRXW WKHVH
FHOOV )LJ $7KLV DQDO\VLV UHYHDOHG WKDW WKH SUHVHQFH RI 7 FHOOV VSHFLILFIRU
PHODQRF\WHOLQHDJHDQWLJHQVLVQRWDVVRFLDWHGZLWKDVXUYLYDOEHQHILWORJUDQN3
6XUYLYDOFXUYHVRISDWLHQWVZLWKHLWKHU0$57RUW\URVLQDVHVSHFLILF7
FHOOVFRPSDUHGZLWKSDWLHQWVZLWKRXWDQ\PHODQRPDVSHFLILF7FHOOVOLNHZLVHGR
QRWVKRZDQ\GHWHFWDEOHVXUYLYDODGYDQWDJH3 DQG3 UHVSHFWLYHO\ )LJ%DQG&7RWHVWZKHWKHUDSRVVLEOHDQWLWXPRUHIIHFWZRXOGPDQLIHVWLWVHOILQ
SDWLHQWVZLWK0$57VSHFLILF7FHOOVGLVSOD\LQJDQHIIHFWRUPHPRU\SKHQRW\SH
VXUYLYDO ZDV DOVR DQDO\]HGIRU WKLV JURXS Q )LJ ' 1R VWDWLVWLFDOO\
VLJQLILFDQWGLIIHUHQFH EHWZHHQ VXUYLYDO RI SDWLHQWV ZLWK HIIHFWRUPHPRU\7 FHOOV
DQGWKRVHZLWKRXWFLUFXODWLQJ7FHOOVZDVREVHUYHGORJUDQN3
,Q VXPPDU\ WKH SUHVHQFH RI PHODQRPDVSHFLILF7 FHOO SRSXODWLRQVLQ SHULSKHUDO
EORRG GRHV QRW OHDG WR D VXUYLYDO EHQHILW IRUSDWLHQWV ZLWK DGYDQFHGVWDJH
PHODQRPD
:HFRQVLGHUHGWKHSRVVLELOLW\WKDWWKHPHODQRPDVSHFLILF7FHOOVZHREVHUYHGFRXOG
KDYHDOLPLWHGFDSDFLW\WRNLOOWXPRUFHOOVIRULQVWDQFHEHFDXVHRIDORZDYLGLW\,Q
VXFKDVFHQDULRDKLJK7FHOOUHVSRQVHZRXOGQRWSUHGLFWDVXEVHTXHQWDQWLWXPRU HIIHFW EXW ZRXOG PHUHO\ EH D UHIOHFWLRQ RI D JURZLQJ WXPRU PDVV7R WHVW WKLV
K\SRWKHVLVSDWLHQWVZHUHGLYLGHGLQWRWKUHHJURXSVWKRVHZLWKGLVHDVHSURJUHVVLRQ
ZLWKLQ PRQWKV DIWHU EORRG VDPSOLQJWKRVH ZLWK VWDEOH GLVHDVH DQG WKRVH ZLWK
SDUWLDOFRPSOHWHUHVSRQVHZLWKLQWKLVWLPHSHULRG:KHQFRPSDULQJWKHVHJURXSV
IRU WKHSUHVHQFH RI FLUFXODWLQJ 0$57VSHFLILF7 FHOOV ZH IRXQG DVWDWLVWLFDOO\
VLJQLILFDQW WZRVLGHG 3 &RFKUDQ$UPLWDJHWUHQG WHVW SUHGRPLQDQFH
RIKLJKQXPEHUV0$57VSHFLILF7FHOOVLQWKHJURXSRISDWLHQWVZLWK
SURJUHVVLYHGLVHDVHLQWKHILUVWPRQWKVDIWHUEORRGVDPSOLQJ7DEOH
,PPXQH(VFDSHWKURXJK/RVVRI+/$$([SUHVVLRQ
7XPRUVPD\HYDGHWKHDFWLRQRIWXPRUVSHFLILF7FHOOVE\GRZQUHJXODWLRQRIHLWKHU
0+&FODVV,FHOOVXUIDFHH[SUHVVLRQRUE\UHGXFLQJDQWLJHQH[SUHVVLRQ7RDGGUHVV
WKLVLVVXHZHH[DPLQHGDQWLJHQDQG+/$$H[SUHVVLRQE\LPPXQRKLVWRFKHPLVWU\
LQ WXPRU PDWHULDOWKDW ZDV DYDLODEOH IURP RQO\ RI WKH SDWLHQWV GDWD QRW VKRZQ$OOPHODQRPDPHWDVWDVHVH[SUHVVHG0$57DQGW\URVLQDVHZKHUHDV
JS H[SUHVVLRQ ZDV KRPRJHQHRXVO\ H[SUHVVHG LQ WXPRUPDWHULDO RI RI
SDWLHQWV7ZHOYHRIWKHVHSDWLHQWVKDGFLUFXODWLQJ0$57VSHFLILF7FHOOV
SDWLHQWVKDGW\URVLQDVHVSHFLILF7FHOOVDQGSDWLHQWKDGJSVSHFLILF7FHOOV
,QRIPHWDVWDVHV+/$$H[SUHVVLRQZDVORVW/DFNRI+/$$H[SUHVVLRQZDV
REVHUYHGLQRIPHWDVWDVHVIURPSDWLHQWVZLWKGHWHFWDEOHPHODQRPDVSHFLILF7
FHOOVDQGRISDWLHQWVZLWKRXWGHWHFWDEOHPHODQRPDVSHFLILF7FHOOV7KHVHGDWD
GHPRQVWUDWH WKDW DOWKRXJK0+& FODVV , ORVV GRHV QRW GLUHFWO\ FRUUHODWH ZLWK WKH
SUHVHQFHRIGHWHFWDEOHWXPRUVSHFLILF7FHOOUHVSRQVHVWKHIUHTXHQWRFFXUUHQFHRI
FODVV,ORVVVXIILFHVWRH[SODLQWKHODFNRIDQWLWXPRUHIIHFWLQDVXEVWDQWLDOIUDFWLRQ
RIWKHDGYDQFHGVWDJHPHODQRPDSDWLHQWV
'LVFXVVLRQ
6HYHUDOJURXSVKDYHUHSRUWHGWKHSUHVHQFHRIQDWXUDOO\RFFXUULQJPHODQRPDVSHFLILF
7FHOOUHDFWLYLW\LQPHODQRPDSDWLHQWVEXWOLWWOHLVNQRZQRQ
WKHWLPHIUDPHRIDSSHDUDQFHDQGHYHQOHVVRQWKHSRVVLEOHUROHRIWKHVHFHOOVLQ
OLPLWLQJWXPRURXWJURZWK7RDGGUHVVWKLVLVVXHZHKDYHH[DPLQHGVSRQWDQHRXV
F\WRWR[LF7FHOOLPPXQLW\DJDLQVWPHODQRVRPDODQWLJHQV0$57W\URVLQDVHDQG
JSLQDODUJHJURXSRIDGYDQFHGVWDJH,9+/$$ SRVLWLYHPHODQRPD
SDWLHQWVDQGKDYHFRUUHODWHGWKHVHUHVSRQVHVZLWKSDWLHQWVXUYLYDO7FHOOUHVSRQVHV
ZHUHDQDO\]HGEHIRUHWKHLQLWLDWLRQRIWUHDWPHQWDQGVKRXOGWKHUHIRUHUHIOHFWWKH
QDWXUDOUHVSRQVHRIWKHLPPXQHV\VWHPWRWKHJURZLQJWXPRUPDVV
7KHVH GDWD GHPRQVWUDWH WKDW LQ DFFRUGDQFH ZLWK RWKHU VWXGLHVVXEVWDQWLDO
H[SDQVLRQVRI&'7FHOOVVSHFLILFIRUPHODQRVRPDODQWLJHQVFDQRFFXULQSDWLHQWV
ZLWKPHWDVWDWLFGLVHDVHDPRXQWLQJXSWRRIWKHWRWDO&'7FHOOSRSXODWLRQ
LQSHULSKHUDOEORRG,PSRUWDQWO\WKHVHKLJKQXPEHUVRIWXPRUVSHFLILF&'7FHOOV
GRQRWKDYHDPHDVXUDEOHSRVLWLYHLQIOXHQFHRQSDWLHQWVXUYLYDO
$OWKRXJK WKH SULPDU\ JRDO RI WKLV VWXG\ ZDV WR HYDOXDWH D SRVWXODWHGEHQHILW RI
VSRQWDQHRXV PHODQRF\WH OLQHDJHVSHFLILF 7FHOO UHVSRQVHVLW PD\ EH XVHIXO WR
GLVFXVVWKHVHGDWDLQUHODWLRQWRLPPXQRWKHUDSHXWLFDSSURDFKHVLQWKLVSDWLHQWJURXS
6HYHUDOPHFKDQLVPVPD\DFFRXQWIRUWKHIDFWWKDWWKH7FHOOSRSXODWLRQVVSHFLILF
IRU WKHVHPHODQRPD DQWLJHQV GR QRW PHDVXUDEO\ LPSLQJH RQ WXPRU JURZWKDQG
GHSHQGLQJ RQ WKH PHFKDQLVP LQYROYHG LPPXQRWKHUDSHXWLFDSSURDFKHV WKDW DLP
WRVWUHQJWKHQWKHVHUHVSRQVHVPD\RUPD\QRWEHZRUWKSXUVXLQJ:HFRQVLGHUHG
WZRPHFKDQLVPV³LPPXQHHVFDSH´DQG³LQVXIILFLHQWQXPEHURUDFWLYLW\RIWXPRU
VSHFLILF7FHOOV
:LWK UHJDUG WR LPPXQH HVFDSH WXPRUV PD\ HYDGH WKH DFWLRQ RIWXPRUVSHFLILF
7 FHOOV E\ GRZQUHJXODWLRQ RI HLWKHU 0+& FODVV, FHOO VXUIDFH H[SUHVVLRQ RU E\
UHGXFLQJ DQWLJHQ H[SUHVVLRQ,Q WKH WXPRU VDPSOHV DYDLODEOH IRU WKLV VWXG\ ZH
IRXQGORVVRI+/$$H[SUHVVLRQLQDVXEVWDQWLDOSRUWLRQRIWKHFDVHVZKHUHDVLQDOO
RIWKHFDVHVDQWLJHQH[SUHVVLRQZDVPDLQWDLQHG7KLVIUHTXHQWRFFXUUHQFHRIFODVV
,ORVVVXIILFHVWRH[SODLQWKHODFNRIDQWLWXPRUHIIHFWLQDVXEVWDQWLDOIUDFWLRQRIWKH
DGYDQFHGVWDJHPHODQRPDSDWLHQWV,QDGGLWLRQLWFDQQRWEHH[FOXGHGWKDWLQSDUWRI
WKHUHPDLQLQJFDVHVHVFDSHIURP7FHOODWWDFNLVDFKLHYHGE\RWKHUPHDQV :LWKUHJDUGWRLQVXIILFLHQWQXPEHURUDFWLYLW\RIWXPRUVSHFLILF7FHOOVLQRI
SDWLHQWVZLWKGHWHFWDEOHWXPRUVSHFLILF7FHOOUHDFWLYLW\WKHUHZDVQRFRQFRPLWDQW
ORVV RI +/$$ RUDQWLJHQ H[SUHVVLRQ ,W LV WHPSWLQJ WR VSHFXODWH WKDW LQ WKHVH SDWLHQWV WKH QXPEHU DQGRU DFWLYLW\ EH LW HLWKHU KRPLQJ FDSDFLW\RU F\WRO\WLF
IXQFWLRQ RI WKH WXPRUVSHFLILF 7 FHOOV ZDV LQVXIILFLHQWWR PHGLDWH D VLJQLILFDQW
DQWLWXPRUHIIHFW%HFDXVHYLWLOLJRLVDVVRFLDWHGZLWKVXFFHVVIXOLPPXQRWKHUDS\
IXUWKHULQGLUHFWHYLGHQFHIRUWKLVQRWLRQLVSURYLGHGE\WKHREVHUYDWLRQWKDWQRQH
RIWKHSDWLHQWVZLWKGHWHFWDEOH7FHOOUHVSRQVHVDJDLQVWPHODQRVRPDODQWLJHQV
VKRZHGVLJQVRIYLWLOLJR/DFNRIYLWLOLJRGHVSLWHVXEVWDQWLDOQXPEHUVRI7FHOOVLQ
VRPHRIWKHSDWLHQWVPD\SRLQWWRIXQFWLRQDOGLIIHUHQFHVEHWZHHQ7FHOOVLQGXFHGE\
LPPXQRWKHUDS\DQGWKHVSRQWDQHRXVUHVSRQVHVREVHUYHGLQWKLVVWXG\
0+&WHWUDPHUVXVHGLQWKLVVWXG\DUHLQGLFDWLYHRIWKH7FHOOUHFHSWRUVSHFLILFLW\
RI WKH GLIIHUHQW PHODQRPDDVVRFLDWHG DQWLJHQVSHFLILF7FHOO SRSXODWLRQV ,W KDV
EHHQGHPRQVWUDWHGWKDW0+&WHWUDPHUELQGLQJGRHVQRWDOZD\VIXOO\FRUUHODWHZLWK
IXQFWLRQDOLW\+RZHYHU LQ RQH SDWLHQW WKH DYDLODEOH EORRG VDPSOHV GLG DOORZ
VLPXOWDQHRXV0+&WHWUDPHUDQGLQWUDFHOOXODU,)1ȖVWDLQLQJ,QWKLVSDWLHQWZLWK
KLJKQXPEHUVRIERWK0$57DQGJSVSHFLILF7FHOOVLQWUDFHOOXODU,)1ȖZDV
SURGXFHGDJDLQVWSHSWLGHSXOVHGWDUJHWFHOOVGLUHFWO\H[YLYR7KLVUHVXOWKRZHYHU
GRHV QRWSUHFOXGH WKH SRVVLELOLW\ WKDW IRU RWKHU SDWLHQWV WKH GHWHFWHGPHODQRPD
VSHFLILF7FHOOSRSXODWLRQVZHUHQRQIXQFWLRQDORUWROHUL]HG
2QWKHEDVLVRIWKHFXUUHQWGDWDLWVHHPVWKDWVSRQWDQHRXVO\RFFXUULQJPHODQRF\WH
OLQHDJHVSHFLILFLPPXQLW\LQVWDJH,9PHODQRPDSDWLHQWVLVODUJHO\DUHIOHFWLRQRI
LQFUHDVLQJWXPRUPDVVDQGVSUHDGLQJDQGVWDJH,9PHODQRPDSDWLHQWVDUHXQOLNHO\
WR EHQHILWIURP WKHVH LPPXQH UHVSRQVHV RWKHU WKDQ LQ H[FHSWLRQDO FDVHV7KHVH
PHODQRPDVSHFLILF7FHOOVPD\EHIXQFWLRQDOO\GLVWLQFWIURP7FHOOVWKDWSOD\DUROH
LQVLWXDWLRQVRIVSRQWDQHRXVUHJUHVVLRQWKDWUDUHO\RFFXULQWKHVHSDWLHQWVRUIURP7
FHOOVWKDWDUHGHWHFWHGRQVXFFHVVIXOLPPXQRWKHUDS\(VFDSHIURPLPPXQLW\E\ORVV
RIH[SUHVVLRQRIWDUJHWPROHFXOHVHLWKHUE\LPPXQHVHOHFWLRQRUJHQHWLFLQVWDELOLW\
RIWXPRUFHOOVIRUPVRQHPDMRUIDFWRUWKDWOLPLWVWKHHIIHFWRIWXPRUVSHFLILF&7/V
LQSDUWRIWKLVDGYDQFHGVWDJHSDWLHQWJURXS,QWKHUHPDLQLQJSDWLHQWVWKHOLPLWHG
HIILFDF\ RI WKH WXPRUVSHFLILF 7FHOO UHVSRQVH PD\ ZHOOEH UHODWHG WR WKH SRRU
TXDOLW\ DQG VXERSWLPDO QXPEHUV RI WXPRUVSHFLILF7 FHOOV DW HDUO\ WLPH SRLQWV
GXULQJWKHGLVHDVH(IIRUWVWRHQKDQFHWKHVHUHVSRQVHVE\YDFFLQDWLRQVWUDWHJLHVRU
WKURXJKDGRSWLYHWKHUDS\DUHWKHUHIRUHZRUWKSXUVXLQJDQGDUHPHHWLQJLQFUHDVLQJ
VXFFHVV
$FNQRZOHGJHPHQWV
:HWKDQN&ROHWWHYDQGHQ%RJDDUGDQG:LOOHNHYDQGHQ.DVWHHOHIRUWKHLUKHOSZLWK
VDPSOH SUHSDUDWLRQ DQG (VWKHU .XHWHU DQG5DTXHO *RPH] IRU SUHSDULQJ 0+&
WHWUDPHUV
7DEOH3DWLHQWFKDUDFWHULVWLFV
122)3$7,(176
0(',$1$*( <55$1*(±<5 6(;
)(0$/(
0$/(
0(7$67$7,&6,7(610(',$1 ±
9,6&(5$/
1219,6&(5$/
6(580/$&7$7('(+<'52*(1$6(0(',$1
75($70(17
'7,&$
7(02=2/20,'(
&+(02%,27+(5$3<
D'7,&GLPHWK\OWULD]HQRLPLGD]ROHFDUER[DPLGH
)LJ3HULSKHUDOEORRGFHOOVZHUHVWDLQHGZLWK+/$$WHWUDPHUVFRQWDLQLQJWKH
W\URVLQDVH±SHSWLGHIROORZHGE\VWDLQLQJZLWKDSDQHORIOLQHDJHDQWLERGLHVDV
GHVFULEHGLQ³3DWLHQWVDQG0HWKRGV´&HOOVZHUHDQDO\]HGE\IORZF\WRPHWU\OHIW
SDQHODQGOLQHDJHDQWLJHQQHJDWLYHDQG0+&WHWUDPHUSRVLWLYHFHOOVZHUHVRUWHG
E\ IOXRUHVFHQFHDFWLYDWHG FHOO VRUWLQJ &HOO VRUWLQJ (QULFKHG 0+& WHWUDPHU
SRVLWLYHOLQHDJHDQWLJHQVQHJDWLYHFHOOVPLGGOHSDQHOZHUHEULHIO\LQFXEDWHGDW
&VWDLQHGZLWK&'PRQRFORQDODQWLERG\DQGUHDQDO\]HGE\IORZF\WRPHWU\
ULJKWSDQHO7\SLFDOO\!RIWKHVHFHOOVDUH&'
)LJ $ UHSUHVHQWDWLYH GRW SORWV RI 0+&WHWUDPHU VWDLQLQJ YHUVXV OLQHDJH
DQWLERGLHV 7RS WKUHH SDQHOV +/$$ PHODQRPD SDWLHQWV +/$$ ZLWK GHWHFWDEOH 0$57± / W\URVLQDVH± ' DQG JS± 9 VSHFLILF &'7 FHOOV LQ SHULSKHUDO EORRG %RWWRP WKUHH SDQHOV FRQWURO VWDLQLQJ
RI+/$$QHJDWLYHPHODQRPDSDWLHQWV+/$$±ZLWK+/$$0$57
W\URVLQDVHDQGJSWHWUDPHU
% VFDWWHU GLDJUDP RI DOO SDWLHQWV ZLWK FLUFXODWLQJ PHODQRPDVSHFLILF 7 FHOOV
VHSDUDWHG E\ DQWLJHQVSHFLILFLW\ 0$57 W\URVLQDVH RU JS 2Q WKH EDVLV
RIWKHOLWHUDWXUHSUHVHQFHRIQDwYH0$57VSHFLILF7FHOOV0$57VS7FHOOV DPRXQWVWRDERXW7PSRVLWLYH0+&WHWUDPHUSRVLWLYH
3$7,(1712 &'5$ &' &'52 &&5
0$57
63(&$7
&(//6
*5283$
1., 17
1., 17
1., 17
1., 17
1., 17
1., 17
1., 17
1.,
1.,
*5283%
1., 17
1., 17
1., 17
1., 17
1., 17
1.,
1.,
1.,
D0$57VSHF0$57VSHFLILFQWQRWWHVWHG
7DEOH1DwYHYHUVXVHIIHFWRUPHPRU\SKHQRW\SHRI0$57VSHFLILF7FHOOV
3DQHODQWLERG\QHJDWLYHDQG0+&WHWUDPHUSRVLWLYH7FHOOVZHUHFRVWDLQHGZLWKWKH
LQGLFDWHGDQWLERGLHV1XPEHUVUHSUHVHQWSHUFHQWDJHVVXUIDFHDQWLJHQSRVLWLYHFHOOV
IURPWRWDO0$57VSHFLILF&'7FHOOV2QWKHEDVLVRIGLIIHUHQWLDOH[SUHVVLRQRI
&'5$&'52DQG&'SDWLHQWVZLWKFLUFXODWLQJ0$57VSHFLILF7FHOOV
FDQEHGLYLGHGLQWRWZRVWDWLVWLFDOO\GLVWLQFWJURXSV$DQG%*URXS$0$57
VSHFLILF 7 FHOOV GLVSOD\LQJ D QDwYH SKHQRW\SH ZLWK KLJK &'5$ :LOFR[RQ
WHVWVLGHG3 KLJK&':LOFR[RQWHVWVLGHG3 DQGORZ
&'52:LOFR[RQWHVWVLGHG3 :KHQWHVWHG&&5H[SUHVVLRQZDV
KLJKVXSSRUWLQJDQDwYHSKHQRW\SH7KHIUHTXHQF\RIWKHVH7FHOOVLQSHULSKHUDO
EORRGLVORZPRVWO\RISHULSKHUDO&'7FHOOSRRO*URXS%0$57
VSHFLILF 7 FHOOV SUHVHQW DW KLJKHU IUHTXHQF\ LQ SHULSKHUDO EORRG PRVWO\
RI &' 7FHOO SRRO GLVSOD\ DQ HIIHFWRUPHPRU\ SKHQRW\SH ZLWK PRVWO\ KLJK
H[SUHVVLRQRI&'52DQGORZ&&5H[SUHVVLRQZKHQWHVWHG
)LJ .DSODQ0HLHU VXUYLYDO FXUYH RI WRWDO FRKRUW RI +/$$ VWDJH ,9
PHODQRPDSDWLHQWV7KHPHGLDQVXUYLYDOLVPRQWKVFRQILGHQFHLQWHUYDO
±PRQWKVZLWKGHDWKV
)LJ.DSODQ0HLHUVXUYLYDOFXUYHVRI+/$$ SDWLHQWVZLWKDQGZLWKRXW
FLUFXODWLQJPHODQRPDVSHFLILF7FHOOV$0$57W\URVLQDVHDQGJSVSHFLILF
&'7FHOOVORJUDQN3 KD]DUGUDWLR>FRQILGHQFHLQWHUYDO&,
±@
%W\URVLQDVHVSHFLILF7FHOOVRQO\ORJUDQN3 KD]DUGUDWLR&,
±&DOO0$57VSHFLILF7FHOOVORJUDQN3 KD]DUGUDWLR
&,±'HVWDEOLVKHGHIIHFWRUPHPRU\0$57VSHFLILF7FHOOVQ
ORJUDQN3
7DEOH ([SDQGHG 0$57VSHFLILF 7 FHOOV SUHIHUHQWLDOO\ LQ SDWLHQWV ZLWK
UDSLG SURJUHVVLYH GLVHDVHD 3DWLHQWV ZHUH GLYLGHG LQWR WKUHH JURXSV GHSHQGLQJ
RQ WKHLU HYDOXDWHG UHVSRQVH WR WZR FRXUVHV RI WUHDWPHQW7UHDWPHQW FRQVLVWHG RI
FKHPRWKHUDS\ ELRWKHUDS\ VHH7DEOH 5HVSRQVHV ZHUH HYDOXDWHG DFFRUGLQJ
WR5(&,67EFULWHULD7KHSUHVHQFHRIH[SDQGHG!0$57VSHFLILFFHOOV
ZDVFRPSDUHGZLWKWKHSUHVHQFHRIQRRUIHZ0$57VSHFLILF7FHOOV
0$5763(&,),&&'7&(//6
5(63216( ! 727$/
&535
6'
3'
727$/
D6WDWLVWLFDODQDO\VLVZDVSHUIRUPHGZLWK&RFKUDQ$UPLWDJHWUHQGWHVW
E5(&,67UHVSRQVHHYDOXDWLRQFULWHULDLQVROLGWXPRUV&535FRPSOHWHRUSDUWLDO
UHVSRQVH6'VWDEOHGLVHDVH3'SURJUHVVLYHGLVHDVH
<HH & 7KRPSVRQ - $ 5RFKH 3 %\UG ' 5 /HH 3 3 3LHSNRUQ
0.HQ\RQ.'DYLV005LGGHOO65DQG*UHHQEHUJ3'0HODQRF\WH
GHVWUXFWLRQDIWHUDQWLJHQVSHFLILFLPPXQRWKHUDS\RIPHODQRPDGLUHFWHYLGHQFHRI
WFHOOPHGLDWHGYLWLOLJR-([S0HG
3KDQ * 4$WWLD 3 6WHLQEHUJ 6 0:KLWH ' ( DQG 5RVHQEHUJ 6
$ )DFWRUV DVVRFLDWHG ZLWK UHVSRQVH WR KLJKGRVH LQWHUOHXNLQ LQ SDWLHQWV ZLWK
PHWDVWDWLFPHODQRPD-&OLQ2QFRO
3KDQ * 4 <DQJ - & 6KHUU\ 5 0 +ZX 3 7RSDOLDQ 6 /
6FKZDUW]HQWUXEHU'-5HVWLIR13+DZRUWK/56HLSS&$)UHH]HU/-
0RUWRQ.(0DYURXNDNLV6$'XUD\3+6WHLQEHUJ60$OOLVRQ-3
'DYLV7$DQG5RVHQEHUJ6$&DQFHUUHJUHVVLRQDQGDXWRLPPXQLW\LQGXFHGE\
F\WRWR[LF7O\PSKRF\WHDVVRFLDWHGDQWLJHQEORFNDGHLQSDWLHQWVZLWKPHWDVWDWLF
PHODQRPD3URF1DWO$FDG6FL86$
'XGOH\ 0 ( :XQGHUOLFK - 5 5REELQV 3 ) <DQJ - & +ZX 3
6FKZDUW]HQWUXEHU ' - 7RSDOLDQ 6 / 6KHUU\ 5 5HVWLIR 1 3 +XELFNL$
0 5RELQVRQ 0 5 5DIIHOG 0 'XUD\ 3 6HLSS &$ 5RJHUV)UHH]HU /
0RUWRQ . ( 0DYURXNDNLV 6$:KLWH ' ( DQG 5RVHQEHUJ 6$ &DQFHU
UHJUHVVLRQDQGDXWRLPPXQLW\LQSDWLHQWVDIWHUFORQDOUHSRSXODWLRQZLWKDQWLWXPRU
O\PSKRF\WHV6FLHQFH
&OHPHQWH&*0LKP0&-U%XIDOLQR5=XUULGD6&ROOLQL3DQG
&DVFLQHOOL 1 3URJQRVWLF YDOXH RI WXPRU LQILOWUDWLQJ O\PSKRF\WHV LQ WKH YHUWLFDO
JURZWKSKDVHRISULPDU\FXWDQHRXVPHODQRPD&DQFHU
0LKP 0 & -U &OHPHQWH & * DQG &DVFLQHOOL 1 7XPRU LQILOWUDWLQJ
O\PSKRF\WHV LQ O\PSK QRGH PHODQRPD PHWDVWDVHV D KLVWRSDWKRORJLF SURJQRVWLF
LQGLFDWRU DQG DQ H[SUHVVLRQ RI ORFDO LPPXQH UHVSRQVH /DE ,QYHVW
%RRQ7&HURWWLQL-&9DQGHQ(\QGH%YDQGHU%UXJJHQ3DQG9DQ
3HO$ 7XPRU DQWLJHQV UHFRJQL]HG E\ 7 O\PSKRF\WHV$QQX 5HY ,PPXQRO
.DZDNDPL<5REELQV3):DQJ5)3DUNKXUVW0.DQJ;DQG
5RVHQEHUJ 6 $ 7KH XVH RI PHODQRVRPDO SURWHLQV LQ WKH LPPXQRWKHUDS\ RI
PHODQRPD-,PPXQRWKHU
/HH 3 3<HH & 6DYDJH 3$ )RQJ / %URFNVWHGW ':HEHU - 6
-RKQVRQ'6ZHWWHU67KRPSVRQ-*UHHQEHUJ3'5RHGHUHU0DQG'DYLV
00&KDUDFWHUL]DWLRQRIFLUFXODWLQJ7FHOOVVSHFLILFIRUWXPRUDVVRFLDWHGDQWLJHQV
LQPHODQRPDSDWLHQWV1DW0HG
3DOHUPR%&DPSDQHOOL50DQWRYDQL6/DQWHOPH(0DQJDQRQL$
0&DUHOOD*'D3UDGD*GHOOD&XQD*55RPDJQH)*DXWKLHU/1HFNHU
$ DQG *LDFKLQR & 'LYHUVH H[SDQVLRQ SRWHQWLDO DQG KHWHURJHQHRXV DYLGLW\ LQ
WXPRUDVVRFLDWHGDQWLJHQVSHFLILF7O\PSKRF\WHVIURPSULPDU\PHODQRPDSDWLHQWV
(XU-,PPXQRO
GH*DVW*&.OXPSHQ+-9\WK'UHHVH)$.HUVWHQ0-9HUUD
1&6HLQ-%DWFKHORU'1RRLMHQ:-DQG6FKRUQDJHO-+3KDVH,WULDO
RIFRPELQHGLPPXQRWKHUDS\ZLWKVXEFXWDQHRXVJUDQXORF\WHPDFURSKDJHFRORQ\
VWLPXODWLQJ IDFWRU ORZGRVH LQWHUOHXNLQ DQG LQWHUIHURQ DOSKD LQ SURJUHVVLYH
PHWDVWDWLF PHODQRPD DQG UHQDO FHOO FDUFLQRPD &OLQ &DQFHU 5HV
$OWPDQ - ' 0RVV 3 $ *RXOGHU 3 - %DURXFK ' + 0F+H\]HU
:LOOLDPV 0 * %HOO - , 0F0LFKDHO $ - DQG 'DYLV 0 0 3KHQRW\SLF
DQDO\VLVRIDQWLJHQVSHFLILF7O\PSKRF\WHV6FLHQFH
9DOPRUL ' )RQWHQHDX - ) /L]DQD & 0 *HUYRLV 1 /LHQDUG '
5LPROGL'-RQJHQHHO9-RWHUHDX)&HURWWLQL-&DQG5RPHUR3(QKDQFHG
JHQHUDWLRQRIVSHFLILFWXPRUUHDFWLYH&7/LQYLWURE\VHOHFWHG0HODQ$0$57
LPPXQRGRPLQDQWSHSWLGHDQDORJXHV-,PPXQRO
0RVVH & $ 0HDGRZV / /XFNH\ & - .LWWOHVHQ ' - +XF]NR (
/6OLQJOXII&/6KDEDQRZLW]-+XQW')DQG(QJHOKDUG9+7KHFODVV
, DQWLJHQSURFHVVLQJ SDWKZD\ IRU WKH PHPEUDQH SURWHLQ W\URVLQDVH LQYROYHV
WUDQVODWLRQLQWKHHQGRSODVPLFUHWLFXOXPDQGSURFHVVLQJLQWKHF\WRVRO-([S0HG
=DURXU+'H6PHW&/HKPDQQ)0DUFKDQG0/HWKH%5RPHUR
3%RRQ7DQG5HQDXOG-&7KHPDMRULW\RIDXWRORJRXVF\WRO\WLF7O\PSKRF\WH
FORQHVGHULYHGIURPSHULSKHUDOEORRGO\PSKRF\WHVRIDPHODQRPDSDWLHQWUHFRJQL]H
DQDQWLJHQLFSHSWLGHGHULYHGIURPJHQH3PHOJS-,QYHVW'HUPDWRO
'DQLHOV0$DQG-DPHVRQ6&&ULWLFDOUROHIRU&'LQ7FHOOUHFHSWRU
ELQGLQJDQGDFWLYDWLRQE\SHSWLGHPDMRUKLVWRFRPSDWLELOLW\FRPSOH[PXOWLPHUV-
([S0HG
&DPSDQHOOL53DOHUPR%*DUEHOOL60DQWRYDQL6/XFFKL31HFNHU
$/DQWHOPH(DQG*LDFKLQR&+XPDQ&'FRUHFHSWRULVVWULFWO\LQYROYHGLQ
0+&SHSWLGHWHWUDPHU7&5ELQGLQJDQG7FHOODFWLYDWLRQ,QW,PPXQRO
'HQNEHUJ*&RKHQ&-DQG5HLWHU<&ULWLFDOUROHIRU&'LQELQGLQJ
RI0+&WHWUDPHUVWR7&5&'DQWLERGLHVEORFNVSHFLILFELQGLQJRIKXPDQWXPRU
VSHFLILF0+&SHSWLGHWHWUDPHUVWR7&5-,PPXQRO
:KHODQ-$'XQEDU353ULFH'$3XUEKRR0$/HFKQHU)2JJ
*6*ULIILWKV*3KLOOLSV5(&HUXQGROR9DQG6HZHOO$.6SHFLILFLW\RI
&7/LQWHUDFWLRQVZLWKSHSWLGH0+&FODVV,WHWUDPHULFFRPSOH[HVLVWHPSHUDWXUH
GHSHQGHQW-,PPXQRO
3LWWHW 0 - 9DOPRUL ' 'XQEDU 3 5 6SHLVHU ' ( /LHQDUG '
/HMHXQH ) )OHLVFKKDXHU . &HUXQGROR 9 &HURWWLQL - & DQG 5RPHUR 3
+LJK IUHTXHQFLHV RI QDLYH 0HODQ$0$57VSHFLILF &'7 FHOOV LQ D ODUJH
SURSRUWLRQRIKXPDQKLVWRFRPSDWLELOLW\OHXNRF\WHDQWLJHQ+/$$LQGLYLGXDOV
-([S0HG
'XWRLW 9 5XELR*RGR\ 9 3LWWHW 0 - =LSSHOLXV $ 'LHWULFK 3 <
/HJDO)$*XLOODXPH35RPHUR3&HURWWLQL-&+RXJKWHQ5$3LQLOOD
&DQG9DOPRUL''HJHQHUDF\RIDQWLJHQUHFRJQLWLRQDVWKHPROHFXODUEDVLVIRU
WKH KLJK IUHTXHQF\ RI QDLYH$0HODQD SHSWLGH PXOWLPHU &'7 FHOOV LQ
KXPDQV-([S0HG
+DPDQQ'%DDUV3$5HS0++RRLEULQN%.HUNKRI*DUGH65
.OHLQ05DQGYDQ/LHU5$3KHQRW\SLFDQGIXQFWLRQDOVHSDUDWLRQRIPHPRU\
DQGHIIHFWRUKXPDQ&'7FHOOV-([S0HG
&KDSPDQ3%(LQKRUQ/+0H\HUV0/6D[PDQ6'HVWUR$1
3DQDJHDV.6%HJJ&%$JDUZDOD666FKXFKWHU/0(UQVWRII06
+RXJKWRQ$1DQG.LUNZRRG-03KDVH,,,PXOWLFHQWHUUDQGRPL]HGWULDORI
WKH'DUWPRXWKUHJLPHQYHUVXVGDFDUED]LQHLQSDWLHQWVZLWKPHWDVWDWLFPHODQRPD-
&OLQ2QFRO
0LGGOHWRQ05*URE--$DURQVRQ1)LHUOEHFN*7LOJHQ:6HLWHU
6*RUH0$DPGDO6&HERQ-&RDWHV$'UHQR%+HQ]06FKDGHQGRUI
' .DSS$:HLVV - )UDDVV 8 6WDWNHYLFK 3 0XOOHU 0 DQG7KDWFKHU 1
5DQGRPL]HGSKDVH,,,VWXG\RIWHPR]RORPLGHYHUVXVGDFDUED]LQHLQWKHWUHDWPHQW
RISDWLHQWVZLWKDGYDQFHGPHWDVWDWLFPDOLJQDQWPHODQRPD-&OLQ2QFRO
.DZDNDPL<1LVKLPXUD0,5HVWLIR137RSDOLDQ6/2¶1HLO%
+6KLO\DQVN\-<DQQHOOL-5DQG5RVHQEHUJ6$7FHOOUHFRJQLWLRQRIKXPDQ
PHODQRPDDQWLJHQV-,PPXQRWKHU
7RSDOLDQ6/+RP66.DZDNDPL<0DQFLQL06FKZDUW]HQWUXEHU
'-=DNXW5DQG5RVHQEHUJ6$5HFRJQLWLRQRIVKDUHGPHODQRPDDQWLJHQVE\
KXPDQWXPRULQILOWUDWLQJO\PSKRF\WHV-,PPXQRWKHU
'¶6RX]D 6 5LPROGL ' /LHQDUG ' /HMHXQH ) &HURWWLQL - & DQG
5RPHUR3&LUFXODWLQJ0HODQ$0DUWVSHFLILFF\WRO\WLF7O\PSKRF\WHSUHFXUVRUV
LQ+/$$PHODQRPDSDWLHQWVKDYHDPHPRU\SKHQRW\SH,QW-&DQFHU
9DOPRUL''XWRLW9/LHQDUG'5LPROGL'3LWWHW0-&KDPSDJQH
3(OOHIVHQ.6DKLQ86SHLVHU'/HMHXQH)&HURWWLQL-&DQG5RPHUR
3 1DWXUDOO\ RFFXUULQJ KXPDQ O\PSKRF\WH DQWLJHQ$ UHVWULFWHG &' 7FHOO
UHVSRQVHWRWKHFDQFHUWHVWLVDQWLJHQ1<(62LQPHODQRPDSDWLHQWV&DQFHU5HV
-DJHU ( 5LQJKRIIHU 0 $UDQG 0 .DUEDFK - -DJHU ' ,OVHPDQQ
& +DJHGRUQ 0 2HVFK ) DQG .QXWK $ &\WRO\WLF 7 FHOO UHDFWLYLW\ DJDLQVW
PHODQRPDDVVRFLDWHG GLIIHUHQWLDWLRQ DQWLJHQV LQ SHULSKHUDO EORRG RI PHODQRPD
SDWLHQWVDQGKHDOWK\LQGLYLGXDOV0HODQRPD5HV
-DJHU ( 1DJDWD < *QMDWLF 6 :DGD + 6WRFNHUW ( .DUEDFK -
'XQEDU35/HH6<-XQJEOXWK$-DJHU'$UDQG05LWWHU*&HUXQGROR
9 'XSRQW % &KHQ < 7 2OG / - DQG .QXWK$ 0RQLWRULQJ &' 7 FHOO
UHVSRQVHV WR 1<(62 FRUUHODWLRQ RI KXPRUDO DQG FHOOXODU LPPXQH UHVSRQVHV
3URF1DWO$FDG6FL86$
<DPVKFKLNRY *7KRPSVRQ / 5RVV: * *DODYRWWL +$TXLOD:
'HDFRQ ' &DOGZHOO - 3DWWHUVRQ - : +XQW ' ) DQG 6OLQJOXII & / -U
$QDO\VLV RI D QDWXUDO LPPXQH UHVSRQVH DJDLQVW WXPRU DQWLJHQV LQ D PHODQRPD
VXUYLYRUOHVVRQVDSSOLFDEOHWRFOLQLFDOWULDOHYDOXDWLRQV&OLQ&DQFHU5HVV
V
5XELR*RGR\9'XWRLW95LPROGL'/LHQDUG'/HMHXQH)6SHLVHU
' *XLOODXPH 3 &HURWWLQL - & 5RPHUR 3 DQG 9DOPRUL ' 'LVFUHSDQF\
EHWZHHQ(/,6327,)1JDPPDVHFUHWLRQDQGELQGLQJRI$SHSWLGHPXOWLPHUVWR
7&5UHYHDOVLQWHUFORQDOGLVVRFLDWLRQRI&7/HIIHFWRUIXQFWLRQIURP7&5SHSWLGH
0+&FRPSOH[HVKDOIOLIH3URF1DWO$FDG6FL86$
<HH & 7KRPSVRQ -$ %\UG ' 5LGGHOO 6 5 5RFKH 3 &HOLV (
DQG*UHHQEHUJ3'$GRSWLYH7FHOOWKHUDS\XVLQJDQWLJHQVSHFLILF&'7FHOO
FORQHVIRUWKHWUHDWPHQWRISDWLHQWVZLWKPHWDVWDWLFPHODQRPDLQYLYRSHUVLVWHQFH
PLJUDWLRQDQGDQWLWXPRUHIIHFWRIWUDQVIHUUHG7FHOOV3URF1DWO$FDG6FL86$
9DOPRUL ' 'XWRLW 9 6FKQXULJHU 9 4XLTXHUH] $ / 3LWWHW 0 -
*XLOODXPH35XELR*RGR\9:DONHU355LPROGL'/LHQDUG'&HURWWLQL
-&5RPHUR3DQG'LHWULFK3<9DFFLQDWLRQZLWKD0HODQ$SHSWLGHVHOHFWV
DQ ROLJRFORQDO 7 FHOO SRSXODWLRQ ZLWK LQFUHDVHG IXQFWLRQDO DYLGLW\ DQG WXPRU
UHDFWLYLW\-,PPXQRO