                         SEQUENCE LISTING

<110>  Yeda Research and Development Co. Ltd.
       AMIT, Ido
       WEINER, Assaf
       KATZENELENBOGEN, Yonatan
       YALIN, Adam
       SHEBAN, Fadi
 
<120>  METHODS OF TREATING CANCER

<130>  85623

<150>  IL 272390
<151>  2020-01-30

<160>  69    

<170>  PatentIn version 3.5

<210>  1
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  1

Gly Asp Ser Ile Ser Asn Tyr Tyr Trp Ser 
1               5                   10  


<210>  2
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  2

Tyr Phe Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  3
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  3

Asp Arg Gly Trp Ala Asp Tyr 
1               5           


<210>  4
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  4

Arg Thr Ser Gln Ser Ile Ser Ser Ser Tyr Leu Ala 
1               5                   10          


<210>  5
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  5

Gly Ala Ser Ser Arg Ala Thr 
1               5           


<210>  6
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  6

Gln Gln Tyr Gly Ser Ser Ile Thr 
1               5               


<210>  7
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  7

Ser Phe Asn Tyr Tyr Trp Ser 
1               5           


<210>  8
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  8

Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Ser Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  9
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  9

Gly Tyr Asn Trp Asn Tyr Phe Asp Tyr 
1               5                   


<210>  10
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  10

Arg Ala Ser Gln Ser Val Asp Asn Asn Leu Val 
1               5                   10      


<210>  11
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  11

Gly Ala Ser Thr Arg Ala Thr 
1               5           


<210>  12
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  12

Gln Gln Tyr Asn Asn Trp Pro Pro Trp Thr 
1               5                   10  


<210>  13
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  13

Gly Phe Ser Leu Ser Ala Gly Gly Val Gly Val Gly 
1               5                   10          


<210>  14
<211>  15
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  14

Leu Ile Tyr Trp Asn Asp Asp Lys Arg Tyr Ser Pro Ser Leu Arg 
1               5                   10                  15  


<210>  15
<211>  13
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  15

Ser His Tyr Asp Tyr Asp Trp Gly Ser Tyr Phe Asp Tyr 
1               5                   10              


<210>  16
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  16

Arg Ser Ser Gln Ser Leu Leu Asp Ser Asp Asp Gly Asn Thr Tyr Leu 
1               5                   10                  15      


Asp 
    


<210>  17
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  17

Thr Leu Ser Tyr Arg Ala Ser 
1               5           


<210>  18
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  18

Met Gln Arg Ile Glu Phe Pro Ile Thr 
1               5                   


<210>  19
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  19

Gly Gly Ser Ile Ser Ser Ala Asn Tyr Tyr Trp Thr 
1               5                   10          


<210>  20
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  20

Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Cys Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  21
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  21

Gly Tyr Asn Trp Asn Tyr Phe Asp Tyr 
1               5                   


<210>  22
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  22

Arg Ala Ser Gln Ser Val Ser Ser Asn Leu Ala 
1               5                   10      


<210>  23
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  23

Gly Ala Ser Thr Arg Ala Thr 
1               5           


<210>  24
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  24

Gln Gln Tyr Asn Lys Trp Pro Pro Trp Thr 
1               5                   10  


<210>  25
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  25

Gly Phe Ala Phe Ser Ser Tyr Gly Met His 
1               5                   10  


<210>  26
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  26

Val Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  27
<211>  18
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  27

Asp Leu Val Val Arg Gly Ile Arg Gly Tyr Tyr Tyr Tyr Phe Gly Met 
1               5                   10                  15      


Asp Val 
        


<210>  28
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  28

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp 
1               5                   10                  15      


<210>  29
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  29

Leu Gly Ser Asn Arg Ala Ser 
1               5           


<210>  30
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  30

Met Gln Gly Leu Gln Thr Pro Ile Thr 
1               5                   


<210>  31
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  31

Gly Phe Thr Phe Ser Asn Tyr Gly Ile His 
1               5                   10  


<210>  32
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  32

Val Ile Trp Phe Asp Gly Arg Asn Lys Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  33
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  33

Asp Pro Phe Asp Tyr Gly Asp Ser Phe Phe Asp Tyr 
1               5                   10          


<210>  34
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  34

Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Ala 
1               5                   10      


<210>  35
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  35

Ala Ala Ser Thr Leu Gln 
1               5       


<210>  36
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  36

Gln Lys Tyr Asn Ser Ala Pro Leu Thr 
1               5                   


<210>  37
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  37

Gly Phe Thr Phe Ser Asp Tyr Tyr Met Thr 
1               5                   10  


<210>  38
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  38

Tyr Ile Ser Ile Ser Gly Ser Ile Thr His Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  39
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  39

Asp Gly Ala Ala Ala Gly Thr Asp Ala Phe Asp Ile 
1               5                   10          


<210>  40
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  40

Arg Ala Ser Gln Asn Val Ser Ser Asn Leu Ala 
1               5                   10      


<210>  41
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  41

Gly Ala Ser Thr Arg Ala Thr 
1               5           


<210>  42
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  42

Gln Gln Tyr His Tyr Trp Pro Thr 
1               5               


<210>  43
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  43

Gly Tyr Thr Phe Thr Gly Phe Tyr Met His 
1               5                   10  


<210>  44
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  44

Trp Ile Asn Pro Asn Ser Gly Gly Thr Tyr Tyr Val Gln Lys Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  45
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  45

Asp Gly Tyr Ser Ser Gly Glu Asp Trp Phe Asp Pro 
1               5                   10          


<210>  46
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  46

Lys Ser Ser Gln Ser Leu Leu His Ser Gly Gly Lys Thr Tyr Leu Tyr 
1               5                   10                  15      


<210>  47
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  47

Glu Val Ser Asn Arg Phe Ser 
1               5           


<210>  48
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  48

Met Gln Ser Ile His Leu Pro Leu Thr 
1               5                   


<210>  49
<211>  230
<212>  PRT
<213>  Artificial sequence

<220>
<223>  An exemplary human TREM-2 amino acid sequence

<400>  49

Met Glu Pro Leu Arg Leu Leu Ile Leu Leu Phe Val Thr Glu Leu Ser 
1               5                   10                  15      


Gly Ala His Asn Thr Thr Val Phe Gln Gly Val Ala Gly Gln Ser Leu 
            20                  25                  30          


Gln Val Ser Cys Pro Tyr Asp Ser Met Lys His Trp Gly Arg Arg Lys 
        35                  40                  45              


Ala Trp Cys Arg Gln Leu Gly Glu Lys Gly Pro Cys Gln Arg Val Val 
    50                  55                  60                  


Ser Thr His Asn Leu Trp Leu Leu Ser Phe Leu Arg Arg Trp Asn Gly 
65                  70                  75                  80  


Ser Thr Ala Ile Thr Asp Asp Thr Leu Gly Gly Thr Leu Thr Ile Thr 
                85                  90                  95      


Leu Arg Asn Leu Gln Pro His Asp Ala Gly Leu Tyr Gln Cys Gln Ser 
            100                 105                 110         


Leu His Gly Ser Glu Ala Asp Thr Leu Arg Lys Val Leu Val Glu Val 
        115                 120                 125             


Leu Ala Asp Pro Leu Asp His Arg Asp Ala Gly Asp Leu Trp Phe Pro 
    130                 135                 140                 


Gly Glu Ser Glu Ser Phe Glu Asp Ala His Val Glu His Ser Ile Ser 
145                 150                 155                 160 


Arg Ser Leu Leu Glu Gly Glu Ile Pro Phe Pro Pro Thr Ser Ile Leu 
                165                 170                 175     


Leu Leu Leu Ala Cys Ile Phe Leu Ile Lys Ile Leu Ala Ala Ser Ala 
            180                 185                 190         


Leu Trp Ala Ala Ala Trp His Gly Gln Lys Pro Gly Thr His Pro Pro 
        195                 200                 205             


Ser Glu Leu Asp Cys Gly His Asp Pro Gly Tyr Gln Leu Gln Thr Leu 
    210                 215                 220                 


Pro Gly Leu Arg Asp Thr 
225                 230 


<210>  50
<211>  470
<212>  PRT
<213>  Artificial sequence

<220>
<223>  exemplary GPNMB (Transmembrane glycoprotein NMB ) amino acid 
       sequence

<400>  50

Lys Arg Phe His Asp Val Leu Gly Asn Glu Arg Pro Ser Ala Tyr Met 
1               5                   10                  15      


Arg Glu His Asn Gln Leu Asn Gly Trp Ser Ser Asp Glu Asn Asp Trp 
            20                  25                  30          


Asn Glu Lys Leu Tyr Pro Val Trp Lys Arg Gly Asp Met Arg Trp Lys 
        35                  40                  45              


Asn Ser Trp Lys Gly Gly Arg Val Gln Ala Val Leu Thr Ser Asp Ser 
    50                  55                  60                  


Pro Ala Leu Val Gly Ser Asn Ile Thr Phe Ala Val Asn Leu Ile Phe 
65                  70                  75                  80  


Pro Arg Cys Gln Lys Glu Asp Ala Asn Gly Asn Ile Val Tyr Glu Lys 
                85                  90                  95      


Asn Cys Arg Asn Glu Ala Gly Leu Ser Ala Asp Pro Tyr Val Tyr Asn 
            100                 105                 110         


Trp Thr Ala Trp Ser Glu Asp Ser Asp Gly Glu Asn Gly Thr Gly Gln 
        115                 120                 125             


Ser His His Asn Val Phe Pro Asp Gly Lys Pro Phe Pro His His Pro 
    130                 135                 140                 


Gly Trp Arg Arg Trp Asn Phe Ile Tyr Val Phe His Thr Leu Gly Gln 
145                 150                 155                 160 


Tyr Phe Gln Lys Leu Gly Arg Cys Ser Val Arg Val Ser Val Asn Thr 
                165                 170                 175     


Ala Asn Val Thr Leu Gly Pro Gln Leu Met Glu Val Thr Val Tyr Arg 
            180                 185                 190         


Arg His Gly Arg Ala Tyr Val Pro Ile Ala Gln Val Lys Asp Val Tyr 
        195                 200                 205             


Val Val Thr Asp Gln Ile Pro Val Phe Val Thr Met Phe Gln Lys Asn 
    210                 215                 220                 


Asp Arg Asn Ser Ser Asp Glu Thr Phe Leu Lys Asp Leu Pro Ile Met 
225                 230                 235                 240 


Phe Asp Val Leu Ile His Asp Pro Ser His Phe Leu Asn Tyr Ser Thr 
                245                 250                 255     


Ile Asn Tyr Lys Trp Ser Phe Gly Asp Asn Thr Gly Leu Phe Val Ser 
            260                 265                 270         


Thr Asn His Thr Val Asn His Thr Tyr Val Leu Asn Gly Thr Phe Ser 
        275                 280                 285             


Leu Asn Leu Thr Val Lys Ala Ala Ala Pro Gly Pro Cys Pro Pro Pro 
    290                 295                 300                 


Pro Pro Pro Pro Arg Pro Ser Lys Pro Thr Pro Ser Leu Ala Thr Thr 
305                 310                 315                 320 


Leu Lys Ser Tyr Asp Ser Asn Thr Pro Gly Pro Ala Gly Asp Asn Pro 
                325                 330                 335     


Leu Glu Leu Ser Arg Ile Pro Asp Glu Asn Cys Gln Ile Asn Arg Tyr 
            340                 345                 350         


Gly His Phe Gln Ala Thr Ile Thr Ile Val Glu Gly Ile Leu Glu Val 
        355                 360                 365             


Asn Ile Ile Gln Met Thr Asp Val Leu Met Pro Val Pro Trp Pro Glu 
    370                 375                 380                 


Ser Ser Leu Ile Asp Phe Val Val Thr Cys Gln Gly Ser Ile Pro Thr 
385                 390                 395                 400 


Glu Val Cys Thr Ile Ile Ser Asp Pro Thr Cys Glu Ile Thr Gln Asn 
                405                 410                 415     


Thr Val Cys Ser Pro Val Asp Val Asp Glu Met Cys Leu Leu Thr Val 
            420                 425                 430         


Arg Arg Thr Phe Asn Gly Ser Gly Thr Tyr Cys Val Asn Leu Thr Leu 
        435                 440                 445             


Gly Asp Asp Thr Ser Leu Ala Leu Thr Ser Thr Leu Ile Ser Val Pro 
    450                 455                 460                 


Asp Arg Asp Pro Ala Ser 
465                 470 


<210>  51
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  51

Phe Ser Asn Tyr Tyr Met Ala 
1               5           


<210>  52
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  52

Ser Leu Thr Asn Ser Gly Gly Ser Thr Tyr 
1               5                   10  


<210>  53
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  53

Glu Trp Ala Gly Ser Gly Tyr 
1               5           


<210>  54
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  54

Asn Val Gly Asn Asn Leu Ala 
1               5           


<210>  55
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  55

Tyr Thr Ser Asn Arg Phe Thr 
1               5           


<210>  56
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Complementarity-determining regions (CDR)

<400>  56

Arg Thr Tyr Asn Ser Pro Trp 
1               5           


<210>  57
<211>  36
<212>  DNA
<213>  Artificial sequence

<220>
<223>  T7 RNA polymerase promoter sequence

<400>  57
scgattgagg ccggtaatac gactcactat aggggc                                 36


<210>  58
<211>  18
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  58
ggagggggtt gaggtgtt                                                     18


<210>  59
<211>  23
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  59
tgtgcacttt tattggtctc aag                                               23


<210>  60
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  60
attatcggag cgcctttctc                                                   20


<210>  61
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  61
agcagaccag ctttcctcag                                                   20


<210>  62
<211>  19
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  62
cccaagtgga acacagcac                                                    19


<210>  63
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  63
gatgctggct gcaagaaact                                                   20


<210>  64
<211>  23
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  64
ccctcacact cagatcatct tct                                               23


<210>  65
<211>  19
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  65
gctacgacgt gggctacag                                                    19


<210>  66
<211>  26
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  66
aaaatcatcc aaaagatact gaacaa                                            26


<210>  67
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  67
ctttggttct tccgttgagg                                                   20


<210>  68
<211>  18
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  68
accctgcagt ggttcgag                                                     18


<210>  69
<211>  19
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  69
cttgcacaag gaagcttgg                                                    19


