Use of anti-sphingosine-1-phosphate antibodies in combination with chemotherapeutic agents

1. A method selected from the group consisting of:

a. a method for treating a cancer associated with sphingosine-1-phosphate (S1P), comprising administering to an animal suffering from cancer a chemotherapeutic agent and an antibody or antigen-binding antibody fragment that neutralizes S1P and thereby treat the cancer;

b. a method for inhibiting tumor growth in an animal having a tumor associated with S1P, comprising administering to the animal a chemotherapeutic agent and an antibody or antigen-binding antibody fragment that neutralizes S1P and thereby inhibit growth of the tumor;

c. a method for inhibiting tumor metastasis in an animal having a tumor associated with S1P, comprising administering to the animal a chemotherapeutic agent and an antibody or antigen-binding antibody fragment that neutralizes S1P and thereby inhibit metastasis of the tumor; and

d. a method for inhibiting the growth of metastatic tumors in an animal having a cancer associated with S1P, comprising administering to the animal a chemotherapeutic agent and an antibody or antigen-binding antibody fragment that neutralizes S1P and thereby inhibit growth of metastatic tumors; wherein said antibody or antigen-binding antibody fragment in any of parts (a)-(d) comprises: (1) a light chain variable domain comprising: (i) a first sequence of amino acid residues of sequence ITTTDIDDDMN (SEQ ID NO: 10); (ii) a second sequence of amino acid residues EGNILRP (SEQ ID NO: 11); and (iii) a third sequence of amino acid residues of sequence LQSDNLPFT (SEQ ID NO: 12); and (2) a heavy chain variable domain comprising: (i) a first sequence of amino acid residues of sequence DHTIH (SEQ ID NO: 13); (ii) a second sequence of amino acid residues of sequence AISPRHDITKYNEMFRG (SEQ ID NO: 16); and (iii) a third sequence of amino acid residues of sequence GGFYGSTIWFDF (SEQ ID NO: 15).

2. A method according to claim 1 wherein the chemotherapeutic agent is an antimitotic agent.

3. A method according to claim 1 wherein the animal is a human.

4. A method according to claim 1 wherein the chemotherapeutic agent is administered in a first composition and the antibody targeted S1P is administered in a second composition.

5. A method according to claim 1 that further comprises surgery and/or radiation to treat cancer.

6. A method according to claim 1 wherein said antibody or antigen-binding antibody fragment in any of parts (a)-(d) comprises:

(1) a light chain variable domain comprising:

ETTVTQSPSFLSASVGDRVTITCITTTDIDDDMNWFQQEPGKAPKLLISEGNI LRPGVPSRFSSSGYGTDFTLTISKLQPEDFATYYCLQSDNLPFTFGQGTKLEI K (SEQ ID NO: 18, residues 21-127, inclusive); and

(2) a heavy chain variable domain comprising:

EVQLVQSGAEVKKPGESLKISCQSFGYIFIDHTIHWMRQMPGQGLEWM GAISPRHDITKYNEMFRGQVTISADKSSSTAYLQWSSLKASDTAMYFCA RGGFYGSTIWFDFWGQGTMVTVSS (SEQ ID NO: 17, residues 20-140, inclusive).

7. A method according to claim 1 wherein said antibody or antigen-binding antibody fragment in any of parts (a)-(d) comprises:

(a) a light chain comprising:

ETTVTQSPSFLSASVGDRVTITCITTTDIDDDMNWFQQEPGKAPKLLISEGNI LRPGVPSRFSSSGYGTDFTLTISKLQPEDFATYYCLQSDNLPFTFGQGTKLEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK SFNRGEC (SEQ ID NO: 24, residues 21-234, inclusive); and

(b)(1) a heavy chain comprising:

EVQLVQSGAEVKKPGESLKISCQSFGYIFIDHTIHWMRQMPGQGLEWMGAI SPRHDITKYNEMFRGQVTISADKSSSTAYLQWSSLKASDTAMYFCARGGF YGSTIWFDFWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 22, residues 20-455, inclusive); or

(b)(1) a heavy chain as recited in part (b)(1) but lacking a C-terminal lysine residue.