Immunoconjugates for the treatment of tumours
A pharmaceutical composition comprising a conjugate of a cytokine and a tumor targeting moiety (TTM) and a pharmaceutically acceptable excipient, wherein the cytokine is present in an amount which does not induce a negative feedback mechanism.
1. A method of diagnosing cancer comprising the steps of:
(a) administering to a patient in need of the same (i) a conjugate of TNFα and at least one tumor targeting moiety (TTM) containing the NGR motif, wherein the conjugate is administered in a dosage range of 5-15 ng/kg, and (ii) a tumor-imaging compound, wherein the conjugate increases the permeability of tumor cells and vessels to the tumor-imaging compound; and
(b) detecting the tumor-imaging compound to determine the presence or absence of a tumor.
2. The method according to claim 1 , wherein the TTM is a tumor vasculature targeting moiety (TVTM).
3. The method according to claim 2 , wherein the TVTM is a binding partner of a tumor vasculature receptor, marker, or other extracellular component.
4. The method according to claim 1 , wherein the TTM is a binding partner of a tumor receptor, marker, or other extracellular component.
5. The method according to claim 1 , wherein the TTM is targeted to aminopeptidase N (CD13).
6. The method according to claim 1 , wherein the TTM is CNGRCVSGCAGRC (SEQ ID NO: 1), NGRAHA (SEQ ID NO: 2), GNGRG (SEQ ID NO: 3), cycloCVLNGRMEC (SEQ ID NO: 16), or linear or cyclic CNGRC (SEQ ID NO: 5 or 17).
7. The method according to claim 1 , wherein the TNFα is linked to the TTM through a spacer.
8. The method according to claim 1 , wherein the TTM is CNGRC (SEQ ID NO: 5) and wherein the amino terminal of TNFα is linked to the CNGRC peptide (SEQ ID NO: 5) through the spacer G (glycine).
9. The method according to claim 1 , wherein the conjugate is in the form of a fusion protein.
10. The method according to claim 1 , wherein the tumor-imaging compound is a radiolabelled antibody.