COMPOSITIONS AND METHODS FOR TREATING CANCER
Methods of detecting, characterizing, and targeting myeloid-derived suppressor cells are disclosed. Some methods include the use of glycan-interacting antibodies, such as anti-STn antibodies. Methods of identifying subjects for treatment with glycan-interacting antibodies are included.
1 . A method of targeting one or more Myeloid-Derived Suppressor Cells (MDSCs) comprising contacting a subject or subject sample with a glycan-interacting antibody, wherein the subject or subject sample includes at least one MDSC.
2 . The method of claim 1 , wherein the glycan-interacting antibody binds to STn.
3 . The method of claim 2 , wherein the glycan-interacting antibody comprises:
a heavy chain variable domain (VH) with an amino acid sequence with at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 1; and
a light chain variable domain (VL) with an amino acid sequence with at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 2.
4 . (canceled)
5 . The method of claim 3 , wherein the glycan-interacting antibody is an IgG antibody.
6 . The method of claim 1 , wherein the one or more MDSC are selected from one or more of a granulocytic lineage cell, a monocytic lineage cell, and an immature lineage cell.
7 . The method of claim 6 , wherein granulocytic lineage cells are preferentially targeted.
8 - 23 . (canceled)
24 . A method of identifying a candidate for anti-STn antibody treatment, the method comprising:
a. obtaining a sample from a subject;
b. identifying one or more MDSC in the sample; and
c. evaluating the one or more MDSC for STn expression using an anti-STn antibody.
25 . The method of claim 24 , wherein the sample is a tumor sample or a fluid sample.
26 . (canceled)
27 . The method of claim 25 , wherein the fluid sample is selected from blood, peripheral blood, spleen, plasma, lymph, saliva, and interstitial fluid.
28 - 29 . (canceled)
30 . The method of claim 24 , wherein the one or more MDSC is selected from a granulocytic MDSC, a monocytic MDSC, and an immature MDSC.
31 . The method of claim 24 , wherein identifying the one or more MDSC in the sample is carried out using at least one of anti-CD33 antibody, anti-HLA-DR antibody, anti-CD45 antibody, anti-CD11b antibody, anti-CD14 antibody, and anti-CD15 antibody.
32 . (canceled)
33 . A method of reducing MDSC levels in at least one tissue and/or fluid from a subject, the method comprising administering an anti-STn antibody to the subject.
34 . The method of claim 33 , wherein the levels of granulocytic MDSCs and/or monocytic MDSCs are reduced.
35 . (canceled)
36 . The method of claim 33 , wherein the at least one tissue comprises tumor tissue and/or spleen tissue.
37 . The method of claim 36 , wherein the at least one tissue comprises a tumor and wherein the percentage of tumor cells expressing STn is reduced by the anti-STn antibody.
38 . The method of claim 33 , wherein the anti-STn antibody comprises:
a heavy chain variable domain (VH) with an amino acid sequence with at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 1; and
a light chain variable domain (VL) with an amino acid sequence with at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 2.
39 . The method of claim 38 , wherein the anti-STn antibody is an IgG antibody.
40 . The method of claim 38 , wherein the anti-STn antibody comprises an antibody-drug conjugate (ADC).
41 . The method of claim 40 , wherein the ADC comprises one or more of an auristatin, a maytansine, a tubulysin, a vinca alkaloid, a pyrrolobenzodiazepine dimer, a camptothecin, a duocarmycin, an amanitin, a PI3K inhibitor, a nucleotide analog, and a MEK inhibitor.
42 . The method of claim 33 , wherein the at least one tissue comprises tumor tissue from one or more of a bladder tumor, a colon tumor, an endometrial tumor, a gastric tumor, a kidney tumor, an ovarian tumor, and a pancreatic tumor.