Combination of an anti ED-B fibronectin domain antibody and gemcitabine

1 . A combination comprising at least (i) a fusion protein and (ii) gemcitabine, wherein the fusion protein in its monomeric form comprises

an antibody-part,

specifically recognising the ED-B-fibronectin domain and

an ε s2 -CH4 domain part.

2 . A combination according to claim 1 ,

wherein the fusion protein in its monomeric form has an N-terminal antibody-part and a C-terminal ε s2 -CH4 part or

wherein the fusion protein in its monomeric form has an N-terminal ε s2 -CH4 part and a C-terminal antibody-part.

3 . A combination according to claim 1 , wherein the fusion protein is present in dimeric form.

4 . A combination according to claim 1 , wherein the antibody-part binds specifically to the ED-B oncofetal fibronectin domain with sub-nanomolar affinity.

5 . A combination according to claim 1 , wherein the antibody-part contains at least one CDR sequence of the L19 antibody.

6 . A combination according to claim 1 , wherein the antibody-part comprises the sequences according to SEQ ID no. 6 to 11

7 . A combination according to claim 1 , wherein the antibody-part comprises at least one V heavy chain according to Seq. Id. No. 01 or at least one V light chain according to Seq. Id. No. 02.

8 . A combination according to claim 1 , wherein the antibody-part comprises one V heavy chain according to Seq. Id. No. 01 and one V light chain according to Seq. Id. No. 02.

9 . A combination according to claim 1 , wherein the heavy and the light chain are connected by an antibody linker.

10 . A combination according to claim 1 , wherein the antibody linker comprises a sequence according to Seq. Id. No. 03, or a sequence having at least 90% identity to the sequence according to SEQ. ID. No. 03.

11 . A combination according to claim 1 , wherein the ε s2 -CH4 domain part is human.

12 . A combination according to claim 1 , wherein the ε s2 -CH4 domain part comprises a sequence according to SEQ. ID. No. 04.

13 . A combination according to claim 1 , wherein a fusion protein linker is connecting the antibody-part and the ε s2 -CH4 domain part.

14 . A combination according to claim 1 , wherein the fusion protein linker has a length of 1 to 6 amino acids.

15 . A combination according to claim 1 , wherein the fusion protein linker comprises a sequence according to SEQ ID No. 05.

16 . A combination according to claim 1 , wherein gemcitabine is gemcitabine hydrochloride.

17 . A combination according to claim 1 , wherein the anti ED-B fibronectin domain antibody is conjugated to a radioisotope.

18 . A combination according to claim 17 , wherein the radioisotope is selected from I; Tc, Re, In, Y, Lu, or I or a mixture thereof.

19 . A combination according to claim 18 , wherein the radioisotope is selected from 123 I, 124 I, 125 I, 131 I, 99m Tc, 186 Re 188 Re 203 Pb 67 Ga, 68 Ga, 43 Sc, 47 Sc, 110m In, 111 In, 97 Ru, 62 Cu, 64 Cu, 67 Cu, 68 Cu, 86 Y, 90 Y, 88 Y, 121 Sn, 153 Sm, 166 Ho, 105 Rh, 177 Lu, 72 Lu and/or 18 F or a mixture thereof.

20 . A combination according to claim 19 , wherein the radioisotope is selected from 131 I.

21 . A combination according to claim 20 , wherein a 131 I-labeled fusion protein is used, and wherein the fusion protein in its monomeric form contains a VI domain of L19, a Vh domain of L19 and an ε s2 -CH4 domain.

22 . A combination according to claim 21 , wherein the fusion protein is 131 I labelled L19-SIP

23 . A combination according to claim 22 , wherein the combination comprises 131 I labelled L19-SIP and Gemcitabine.

24 . A combination according to claim 1 , for use as a medicament.

25 . A combination according to claim 1 , for use as a medicament for the treatment of cancer.

26 . A combination according to claim 25 , wherein the cancer is selected from non-small cell lung cancer, head and neck cancer, ovarian cancer and breast cancer.

27 . A combination according to claim 26 , wherein the cancer is pancreatic cancer.

28 . A method of treating cancer in a patient in need of such treatment which method includes the administration of a combination according to claim 1 .