Tumor-specific recognition molecules
The invention relates to recognition molecules which are directed towards tumors and can be used in the diagnosis and therapy of tumor diseases.
1. A recombinant recognition molecule comprising variable heavy (VH) and variable light (VL) antibody framework sequences and complementarity determining regions (CDRs) comprising the amino acid sequences set forth in
(i) the amino acid sequence SEQ ID NO. 1,
(ii) the amino acid sequences SEQ ID NO.2 or 3,
(iii) the amino acid sequence SEQ ID NO.4, 5 or 6,
(iv) the amino acid sequence SEQ ID NO.7 or 8 or 9,
(v) the amino acid sequence SEQ ID NO. 10 or 11, and
(vi) the amino acid sequence SEQ ID NO. 12 or 13,
wherein the antibody framework sequences
a) FRH1, FRH2, FRH3 and FRH4 for the variable heavy chain VH are the following amino acid sequences, the amino acid position corresponding to the numbering according to Kabat:
for FRH1 in position
1
Q or E
2
V
3
Q, K or T
4
L
5
K or V
6
E or Q
7
S
8
G
9
A
10
E
11
L or V
1.2
V or K
13
R or K
14
P
15
G
16
T or A
17
S
18
V
19
K
20
I or V
21
S or P
22
C
23
K
24
A, V, S or T
25
S
26
G
27
Y, F, S or D
28
T
29
F, L or I
30
T
for FRH2 in position
36
W
37
V
38
K or R
39
Q
40
R or A
41
P
42
G
43
H or Q
44
G
45
L
46
E
47
W or R
48
I or M
49
G
for FRH3 in position
66
K or R
67
A or V
68
T
69
L or M
70
T
71
A, L or T
72
D
73
T
74
S
75
S or T
76
S
77
T
78
A
79
Y
80
M
81
Q or E
82
L
82a
S
82b
S or R
82c
L
83
T or R
84
S
85
E
86
D
87
S or T
88
A
89
V
90
Y
91
F or y
92
C
93
A
94
Y, K or R
for FRH4 in position
103
W
104
G
105
Q
106
G
107
T
108
T, S or L
109
V or L
110
T
111
V
112
S
113
S or A
b) FRL1, FRL2, FRL3 and FRL4 for the variable light chain VT, are the following amino acid sequences, the amino acid position corresponding to the numbering according to Kabat:
for FRL1 in position
1
D
2
I, V or L
3
Q or L
4
M
5
T
6
Q
7
T or S
8
P
9
L
10
S
11
L
12
P
13
V
14
S or T
15
L or P
16
G
17
D or E
18
Q or P
19
A
20
S
21
I
22
S
23
C
for FRL2 in position
35
W
36
Y
37
L
38
Q
39
K
40
P
41
G
42
Q
43
S
44
P
45
K or Q
46
L
47
L
4B
I or V
49
Y
for FRL3 in position
57
G
58
V
59
P
60
D
61
R
62
F
63
S
64
G
65
S
66
G
67
S
68
G
69
T
70
D
71
F
72
T
73
L
74
K
75
I
76
S
77
R
78
V
79
E
80
A
81
E
82
D
83
L or V
84
G
85
V
86
Y
87
Y
88
C
for FRL4 in position
98
F
99
G
100
G or Q
101
G
102
T
103
K
104
L
105
E
106
I or L
106a
K
107
R
108
A.
and which specifically binds to the core 1 antigen.
2. A construct comprising the recombinant recognition molecules according to claim 1 , further comprising (i) immunoglobulin domains of various species, (ii) enzyme molecules, (iii) signal sequences, (iv) fluorescent dyes, (v) toxins, (vi) one or more antibodies or antibody fragments with different specificity, (vii) cytolytic components, (viii) immunomodulators, (ix) immunoeffectors, (x) chelating agents for radioactive labeling, (xi) radioisotopes, and/or (xii) liposomes.
3. A method for the diagnosis, reduction, therapy, follow-up or aftercare of a core-1 positive tumor disease or a core-1 positive metastasis, comprising administering to a subject in need thereof, a recognition molecule comprising variable heavy (VH) and variable light (VL) antibody framework sequences and complementarity determining regions (CDRs) comprising the amino acid sequences set forth in
(i) the amino acid sequence SEQ ID NO. 1,
(ii) the amino acid sequences SEQ ID NO.2 or 3,
(iii) the amino acid sequence SEQ ID NO.4, 5 or 6,
(iv) the amino acid sequence SEQ ID NO.7 or 8 or 9,
(v) the amino acid sequence SEQ ID NO. 10 or 11, and
(vi) the amino acid sequence SEQ ID NO. 12 or 13,
and which specifically binds to the core 1 antigen.
4. The method according to claim 3 , wherein the recognition molecule is a non-labeled recognition molecule, which is an IgM or IgG or is a molecule derived therefrom.
5. The method according to claim 3 , wherein the recognition molecules are multibody.
6. A method for the diagnosis, reduction, therapy, follow-up or aftercare of a core-1 positive tumor disease or a core-1 positive metastasis, comprising administering to a subject in need thereof, a construct according to claim 2 .