Targeted theranostics for metastatic prostate cancer
OwnerLaurel O. Sillerud, David L. Vander Jagt +1inventors
InventorsLaurel O. Sillerud, David L. Vander Jagt, Lorraine Deck
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Abstract
The present invention relates to methods of diagnosing and treating prostate cancer, including metastatic prostate cancer. Related pharmaceutical compositions are also provided.
Claims52
An immunocelle for treating prostate cancer comprising:
- (a) a particulate core comprising a mixture of superparamagnetic particles and at least one active ingredient which is active for treating prostate cancer, said core being encapsulated by a plurality of phospholipds comprising at least one pegylated phospholipid, a phospholipid comprising conjugation functionalities and, optionally, a cross-linking agent;
- and
- (b) a prostate cancer cell targeting monoclonal or polyclonal antibody which is conjugated to said particulate core through an appropriate functionality of the conjugatable phospholipid.
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A method of diagnosing the presence and/or progression of anti-cancer treatment in a subject of prostate cancer comprising:
- (a) administering a pharmaceutical formulation of the invention to the subject;
- (b) subjecting the subject to magnetic resonance imaging;
- and
- (c) determining through MRI contrast enhancement whether the subject suffers from prostate cancer and in particular, metastatic prostate cancer by comparing the resulting MRI image from the subject with a control or standard (which may be a disease control or a normal/healthy control to which the subject's MRI image may be compared for diagnosis).
A composition comprising a population of immunocells for treating prostate cancer, including metastatic prostate cancer, said immunoecelle comprising:
- (a) a particulate core comprising an effective amount of an anticancer agent, optionally in combination with a NF-κB pathway inhibitor and further optionally in combination with a mixture of superparamagnetic particles, said core being encapsulated by a plurality of phospholipds comprising at least one pegylated phospholipid, a phospholipid comprising conjugation functionalities, and further optionally, a cross-linking agent, including a cross-linking phospholipid;
- (b) a targeting antibody or peptide or other binding motif which is selected from the group consisting of prostate cancer cell targeting monoclonal or polyclonal antibody which is/are conjugated to said particulate core through an appropriate functionality of the conjugatable phospholipid.
The composition according to claim wherein 8 wherein said anticancer agent is a taxane which is combined with a NF-κB pathway inhibitor.
A method of determining the existence of cancer tissue in a patient comprising administering to said patient an effective amount of a population of paramagentic nanoparticles and subjecting said nanoparticles to NMR relaxometry to determine the volumetric quantitative MRI measurement of any superparamagnetic nanoparticle in biological tissues.
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A multifunctional superparamagnetic iron platinum nanoparticle (SIPP) comprising:
- (a) two or more prostate cancer cell surface markers selected from the group consisting of prostate specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), the integrin αvβ3, and the neurotensin receptor (NTR);
- and
- (b) one or more active ingredients selected from the group consisting of paclitaxel, docetaxel, ca27, DHA-paclitaxel, BAY 11-7082, SN-50, and one or more of the following compounds:
A stealth immunomicelle that specifically targets a human prostate cancer cell line and that is dectable by either MRI or fluorescence imaging, the immunomicelle comprising a multifunctional superparamagnetic iron platinum nanoparticle that:
- (a) is encapsulated by polyethyleneglycolated and rhodamine-conjugated, distearoyl-phosphatidyl-ethanolamine (DSPE);
- and
- (b) contains one or more prostate cancer cell surface markers selected from the group consisting of prostate specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), the integrin αvβ3, and the neurotensin receptor (NTR).
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A stealth immunomicelle that specifically targets a human prostate cancer cell line and that is dectable by either MRI or fluorescence imaging, the immunomicelle comprising a multifunctional superparamagnetic iron platinum nanoparticle that:
- (a) is encapsulated by polyethyleneglycolated and rhodamine-conjugated, distearoyl-phosphatidyl-ethanolamine (DSPE);
- and
- (b) contains one or more prostate cancer cell surface markers selected from the group consisting of prostate specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), the integrin αvβ3, and the neurotensin receptor (NTR) and J591;
- wherein the superparamagnetic iron platinum nanoparticle has a core diameter of between about 5 nm to about 50 nm and the immunomicelle has a transverse relaxivity measured at 4.7 Tesla of between about 250 Hz mM−1 to about 350 Hz mM−1.
A PSMA-targeted nanoplex comprising:
- (a) a radiolabel for detection;
- (b) a siRNA delivery vector comprising a siRNA which downregulates a specific pathway;
- (c) a prodrug-activating enzyme that synthesizes a cytotoxic drug locally from a systemically administered nontoxic drug at a site targeted by the nanoplex;
- and
- (d) a PSMA targeting moiety.
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A PEGylated stealth immunomicelle comprising:
- (a) a particulate core comprising a mixture of superparamagnetic particles and at least one bioactive agent or drug comprising a lipid-modified drug selected from the group consisting of anti-cancer active agents and active agents useful in the treatment of prostate cancer, said core being encapsulated by a plurality of phospholipds comprising at least one pegylated phospholipid, a phospholipid comprising conjugation functionalities, and optionally, a fluorescence-inducing (fluorescent) phospholipid, and/or a cross-linking agent, including a cross-linking phospholipid;
- and
- (b) a targeting antibody or peptide or other binding motif which is selected from the group consisting of a prostate cancer targeting monoclonal or polyclonal antibody and a monoclonal or polyclonal antibody or a peptide which targets prostate specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), the integrin αvβ3, and the neurotensin receptor (NTR) and which is/are conjugated to said particulate core through an appropriate functionality of the conjugatable phospholipid.
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Dependencies are inferred from the claim text.