Methods and reagents for tumor targeting with greater efficacy and less toxicity
The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.
1. A method for treating prostate cancer in a subject, the method comprising co-administering to a subject in need thereof, a therapeutically effective amount of J591-Ac 225 and a therapeutically effective amount of a PSMA-Lu 177 peptide, wherein said administering is carried out to deliver the J591-Ac 225 and the PSMA-Lu 177 peptide, to prostate cancer tissue, at a radiobiologically effective dose greater than that achieved by administration of the maximum tolerated dose of either the J591-Ac 225 or the PSMA-Lu 177 peptide alone, without increasing toxicity in normal tissue beyond that resulting from administration of the maximum tolerated dose of either the J591-Ac 225 or the PSMA-Lu 177 peptide alone.
2. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 peptide are co-administered in a single dosage form.
3. The method of claim 1 , wherein the J591-Ac 225 and PSMA-Lu 177 peptide are administered in separate dosage forms.
4. The method of claim 1 , wherein the PSMA-Lu 177 peptide is PSMA I&T-Lu 177 .
5. The method of claim 4 , wherein J591-Ac 225 and PSMA I&T-Lu 177 are administered to the subject by injection.
6. The method of claim 5 , wherein the injection to the subject is by intravenous administration.
7. The method of claim 4 , wherein said co-administration is via simultaneous administration, sequential administration, continuous administration, or a combination thereof to the subject.
8. The method of claim 4 , wherein J591-Ac 225 and PSMA I&T-Lu 177 are co-administered to the subject to allow for J591-Ac 225 and PSMA I&T-Lu 177 to be dosed at about 25% to about 100% of their respective maximum tolerated doses.
9. The method of claim 4 , wherein the J591-Ac 225 and/or PSMA I&T-Lu 177 are administered to the subject in multiple doses per day.
10. The method of claim 4 , wherein J591-Ac 225 and PSMA I&T-Lu 177 are dosed and co-administered to the subject to achieve appropriate systemic levels for J591-Ac 225 and PSMA I&T-Lu 177 in the subject.
11. The method of claim 4 , wherein PSMA I&T-Lu 177 is administered at a dose of about 300 to 500 mCi total in a 2 week cycle.
12. The method of claim 4 , wherein J591-Ac 225 and PSMA I&T-Lu 177 are dosed and administered to the subject so that both J591-Ac 225 and PSMA I&T-Lu 177 target PSMA concurrently.
13. The method of claim 1 , wherein the subject is a human.
14. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 are co-administered to the subject to allow for J591-Ac 225 and PSMA-Lu 177 to be dosed at 100% of their respective maximum tolerated doses.
15. The method of claim 1 , wherein the J591-Ac 225 is administered to the subject at 100% of its maximum tolerated dose.
16. The method of claim 1 , wherein the PSMA-Lu 177 is administered at 100% of its maximum tolerated dose.
17. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 are independently administered at a dose of greater than 75% of their respective maximum tolerated doses.
18. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 are independently administered at a dose of greater than 80% of their respective maximum tolerated doses.
19. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 are independently administered at a dose of greater than 85% of their respective maximum tolerated doses.
20. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 are independently administered at a dose of greater than 90% of their respective maximum tolerated doses.
21. The method of claim 1 , wherein the J591-Ac 225 and the PSMA-Lu 177 are independently administered at a dose of greater than 95% of their respective maximum tolerated doses.