Prostate-specific membrane antigen (PSMA)-binding peptides and method of use

Abstract

An anti-PSMA peptide includes an STMG (SEQ ID N0;2) motif or a structurally similar PSMA-binding variant thereof. The anti-PSMA peptide may be used as a targeting domain in, for example, a multi specific compound, chimeric antigen receptor (CAR) compound, a targeted immunotherapeutic compound, a targeted therapeutic compound, a targeted imaging compound, or as a capture moiety immobilized to a substrate in an assay device. Compounds that include the anti-PSMA peptide can be used in methods of treating a disease (e.g., cancer) in subject, methods of detecting cells that express PSMA, and / or methods of isolating cells that express PSMA.

Description

[0001]PCT Patent Application Attorney Docket No.0110.000728WO01 PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)-BINDING PEPTIDES AND METHOD OF USE CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application Serial No. 63 / 547,517, filed on November 6, 2023, the disclosure of which is incorporated by reference herein in its entirety. GOVERNMENT FUNDING This invention was made with government support under CA196215 awarded by the National Institutes of Health. The government has certain rights in the invention. SEQUENCE LISTING This application contains a Sequence Listing electronically submitted via Patent Center to the United States Patent and Trademark Office as an .xml file entitled “0110-000728WO01.xml” having a size of 12 kilobytes and created on October 31, 2024. The information contained in the Sequence Listing is incorporated by reference herein. SUMMARY This disclosure describes, in one aspect, an anti-PSMA peptide that includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In another aspect, this disclosure describes a multispecific compound that includes a targeting domain and an immune cell engaging domain operably linked to the targeting domain. The targeting domain includes an anti-PSMA polypeptide. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the immune cell is a T cell or a natural killer (NK) cell. In one or more embodiments where the immune cell is an NK cell, the immune cell engaging domain includes a ligand or antibody that specifically binds to CD16. In one or more embodiments where the immune cell is an NK cell, the multispecific compound further includes an NK cell activating domain. In another aspect, this disclosure describes an isolated nucleic acid sequence encoding any embodiment of a multispecific compound that includes an anti-PSMA polypeptide. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In another aspect, this disclosure describes a host cell that includes any embodiment of a nucleic acid that encodes any embodiment of a multispecific compound that includes an anti- PSMA polypeptide. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more of these embodiments, the host cell is a T cell, an NK cell, or a macrophage. In another aspect, this disclosure describes a pharmaceutical composition that includes any embodiment of a multispecific compound that includes an anti-PSMA polypeptide and a pharmaceutically acceptable carrier. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In another aspect, this disclosure describes a method that generally includes administering to a subject a multispecific compound in an amount effective to induce natural killer (NK)-mediated killing of a cell. Generally, the multispecific compound includes an anti- PSMA peptide and an NK engaging domain operably linked to the targeting domain. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In one or more embodiments, the multispecific compound further includes an immune cell activating domain. In another aspect, this disclosure describes a method for stimulating expansion of natural killer (NK) cells in vivo. Generally, the method includes administering to a subject a multispecific compound in an amount effective to induce natural killer (NK)-mediated killing of a cell. Generally, the multispecific compound includes an anti-PSMA peptide and an NK engaging domain operably linked to the targeting domain. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In one or more embodiments, the multispecific compound further includes an immune cell activating domain. In another aspect, this disclosure describes a method for treating a subject having, or at risk of having cancer. Generally, the method includes administering to a subject a multispecific compound in an amount effective to induce natural killer (NK)-mediated killing of a cell. Generally, the multispecific compound includes an anti-PSMA peptide and an NK engaging domain operably linked to the targeting domain. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In one or more embodiments, the multispecific compound further includes an immune cell activating domain. In one or more embodiments, the cancer cells express PSMA. In one or more embodiments, the cancer includes prostate cancer, salivary gland cancer, thyroid cancer, hepatocellular carcinoma, renal cell carcinoma, glioblastoma, breast cancer, or lung cancer. In one or more embodiments, the multispecific compound is administered prior to, simultaneously with, or following chemotherapy, surgical resection of a tumor, or radiation therapy. In one or more of these embodiments, the chemotherapy includes altretamine, amsacrine, L-asparaginase, colaspase, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytophosphane, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fluorouracil, fludarabine, fotemustine, ganciclovir, gemcitabine, hydroxyurea, idarubicin, ifosfamaide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitoxantrone, mitomycin C, nimustine, oxaliplatin, paclitaxel, pemetrexed, procarbazine, raltitrexed, temozolomide, teniposide, tioguanine, thiotepa, topotecan, vinblastine, vincristine, vindesine, or vinorelbine. In another aspect, this disclosure describes a chimeric antigen receptor (CAR) compound that includes an anti-PSMA peptide. Generally, the anti-PSMA polypeptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In another aspect, this disclosure describes a targeted immunotherapy compound. Generally, the targeted immunotherapy compound includes a targeting domain and an immunotherapeutic domain linked to the targeting domain. The targeting domain includes an anti-PSMA peptide. Generally, the anti-PSMA peptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In another aspect, this disclosure describes a targeted therapeutic compound that includes a targeting domain and a therapeutic domain linked to the targeting domain. The targeting domain includes an anti-PSMA peptide. Generally, the anti-PSMA peptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In one or more embodiments, the therapeutic domain includes a drug, a therapeutic radioisotope, a toxin, a cytokine, or a chemokine. In another aspect, this disclosure describes a targeted imaging compound that includes a targeting domain and an imaging domain linked to the targeting domain. The targeting domain includes an anti-PSMA peptide. Generally, the anti-PSMA peptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. In one or more embodiments, the imaging domain includes a colorimetric label, a fluorescent label, a radioactive label, a magnetic label, or an enzymatic label. In another aspect, this disclosure describes a capture assay device that includes an anti- PSMA peptide immobilized to a substrate. Generally, the anti-PSMA peptide includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. In one or more embodiments, the anti-PSMA peptide includes any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14. The above summary is not intended to describe each disclosed embodiment or every implementation of the present invention. The description that follows more particularly exemplifies illustrative embodiments. In several places throughout the application, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list. BRIEF DESCRIPTION OF THE FIGURES The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. FIG.1. In vivo antitumor activity of STMG-Ad with systemic injection. FIG.2. In vivo antitumor activity and virus replication of STMG-Ad. (A) Relative tumor volume. (B) Absolute tumor volume. FIG.3. In vivo antitumor activity of wild-type Ad5 or STMG-Ad in mice having tumors implanted on the right or left side. FIG.4. Fluorescence microscopy showing expression of the virus structural protein hexon in cells infected with wild-type Ad5 or STMG-Ad. Images shown at 10× magnification. FIG.5. Fluorescence microscopy showing expression of the virus structural protein hexon in cells infected with wild-type Ad5 or STMG-Ad. Images shown at 4× magnification. FIG.6. Replication and cytocidal activity of PSMA-targeted adenovirus in vitro. (A) Viral copy number detected in PC3 or CWR22Rv1 cells infected with STMG-Ad. (B) Images of viable cells infected with STMG-Ad at three multiplicities of infection. FIG.7. Cell killing activity of STMG-Ad in DU145 or CWR22Rv1 cells eight days after infection. DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS This disclosure generally describes various platforms that employ a peptide that targets and / or selectively binds to prostate-specific membrane antigen (PSMA). Prostate-specific membrane antigen (PSMA) is over-expressed on the membrane of aggressive forms of prostate cancer, other human cancers, and endothelial cells of tumor neovasculature. PSMA can be engineered into T cells as a reporter for imaging or targeted killing. Selection of peptides that target and / or defectively bind to PSMA are described in U.S. Provisional Patent Application 63 / 462,754, filed April 28, 2023, entitled “TARGETED ADENOVIRUSES AND METHODS OF USING”. This disclosure describes proteins, compounds, and devices that includes an anti-PSMA peptide, and methods of using such proteins, compounds, or devices. Exemplary technology platforms in which an anti-PSMA peptide may be used include, but are not limited to, chimeric antigen receptor therapies (e.g., CAR-NK therapy, CAR-T therapy, CAR-macrophage therapy, etc.), multispecific immune cell engager technologies (e.g., bispecific killer engagers, trispecific killer engagers, bispecific T cell engagers, trispecific T cell engagers, etc.), targeted immunotherapies (e.g., targeted ADAM17 blocker (TAB) therapy), delivery of therapeutics (e.g., antibody-drug conjugates, delivery of therapeutic radioisotopes, delivery of toxins, delivery of cytokines, delivery of chemokines), imaging technologies (delivery of labeling constructs and / or labeling radioisotopes), or cell and / or ligand capture technologies (e.g., ELISA, etc.). Thus, in one aspect, this disclosure describes anti-PSMA peptides that include an STMG (SEQ ID NO:2) motif or a PSMA-binding variant thereof. Exemplary anti-PSMA peptides are provided in SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14. In another aspect, this disclosure describes a multispecific compound that includes an anti-PSMA peptide. Generally, the multispecific compound includes a targeting domain that includes the anti-PSMA peptide. The multispecific compound can further include one or more additional functional domains. Thus, the anti-PSMA peptide may be one domain of a multispecific compound such as, but not limited to, a bi-specific Killer engager molecule (BiKE), a tri-specific Killer engager molecule (TriKE), a tetra-specific Killer engager molecule, a penta-specific Killer engager molecule, a bi-specific T cell engager molecule, a tri-specific T cell engager molecule, a tetra-specific T cell engager molecule, a penta-specific T cell engager molecule, a chimeric antigen receptor (CAR, for expression in, for example, CAR T cells, CAR NK cells, CAR macrophage cells, etc.), a full antibody construct (e.g., to induce antibody- dependent cellular toxicity (ADCC)), an antibody-drug conjugate (ADC) molecule (e.g., for delivery of a toxin), a labeling construct (e.g., for commercial evaluation of antigen expression), a radiolabeled format (e.g., for positron-emission tomography (PET) imaging or directed radiation delivery), applications for delivery of a cytokine and / or a chemokine, or other general immunotherapeutic approach. In another aspect, this disclosure describes a capture assay device that includes an anti- PSMA polypeptide immobilized to a substrate. Anti-PSMA binding motifs Anti-PSMA binding motifs were identified as described in U.S. Provisional Patent Application No.63 / 462,754, filed April 28, 2023. Briefly, anti-PSMA binding motifs were identified from AB-loop fiber-modified adenovirus library clones that targeted PSMA- expressing tumors. Mice were implanted with subcutaneous CWR22Rv1 tumors. CWR22Rv1 cells are a prostate tumor cell line and are known to express PSMA. Each mouse was then treated with 5×106viral particles via intravenous injection. The replication-competent adenovirus allowed for the rapid spreading of the most efficient viruses in the library in subsequent replication steps, thereby leading to an effective enrichment of such viruses. The DNA region containing the AB-loop mutant of adenovirus recovered from the tumors was then amplified by PCR. DNA sequencing of the PCR products revealed enrichment of several candidates, and the most abundant consensus sequence of selection was STMGTSH (SEQ ID NO:3). Table 1. Motifs related to the STMGTSH motif Amino acid position SEQ ID NO 1 2 3 4 5 6 7 , p p sequence of any one of SEQ ID NOs:2-14 or a structurally similar PSMA-binding variant thereof. SEQ ID NOs:2-14, set forth in Table 1, provide exemplary PSMA-binding variants. As used herein, a peptide is “structurally similar” to a reference peptide if the amino acid sequence of the peptide possesses a specified amount of identity compared to the reference peptide. Structural similarity of two peptides can be determined by aligning the residues of the two peptides (for example, a candidate peptide and any one of SEQ ID NOs:2-14) to optimize the number of identical amino acids along the lengths of their sequences; gaps in either or both sequences are permitted in making the alignment in order to optimize the number of identical amino acids, although the amino acids in each sequence must nonetheless remain in their proper order. A candidate peptide is the peptide being compared to the reference peptide. A candidate peptide can be isolated, for example, from an animal, or can be produced using recombinant techniques, or chemically or enzymatically synthesized. A pair-wise comparison analysis of amino acid sequences can be carried out using the BESTFIT algorithm in the GCG package (version 10.2, Madison WI). Alternatively, peptides may be compared using the Blastp program of the BLAST 2 search algorithm, as described by Tatiana et al., (FEMS Microbiol Lett, 174, 247-250 (1999)), and available on the National Center for Biotechnology Information (NCBI) website. The default values for all BLAST 2 search parameters may be used, including matrix = BLOSUM62; open gap penalty = 11, extension gap penalty = 1, gap x_dropoff = 50, expect = 10, wordsize = 3, and filter on. In the comparison of two amino acid sequences, structural similarity may be referred to by percent “identity” or may be referred to by percent “similarity.” “Identity” refers to the presence of identical amino acids. “Similarity” refers to the presence of not only identical amino acids but also the presence of conservative substitutions. A conservative substitution for an amino acid in an anti-PSMA peptide may be selected from other members of the class to which the amino acid belongs. For example, it is well-known in the art of protein biochemistry that an amino acid belonging to a grouping of amino acids having a particular size or characteristic (such as charge, hydrophobicity, and hydrophilicity) can be substituted for another amino acid without altering the activity of a protein, particularly in regions of the protein that are not directly associated with biological activity. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and tyrosine. Polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, or glutamine. The positively charged (basic) amino acids include arginine, lysine, or histidine. The negatively charged (acidic) amino acids include aspartic acid or glutamic acid. Conservative substitutions include, for example, Lys for Arg or vice versa to maintain a positive charge; Glu for Asp or vice versa to maintain a negative charge; Ser for Thr or vice versa so that a free -OH is maintained; or Gln for Asn or vice versa to maintain a free -NH2. Likewise, biologically active analogs of a peptide containing deletions or additions of one or more contiguous or noncontiguous amino acids that do not eliminate a functional activity of the peptide are also contemplated. An anti-PSMA peptide as described herein can include a peptide segment with at least 71%, at least 75%, or at least 85% sequence similarity to the reference amino acid sequence. Alternatively, an anti-PSMA peptide as described herein can include a peptide segment with at least 71%, at least 75%, or at least 85% sequence identity to the reference amino acid sequence. As used herein, reference to a “peptide segment” means that the anti-PSMA motif can be included in a larger polypeptide. In the context of determining whether a candidate peptide is an anti-PSMA peptide, the sequence identity or similarity is determined only with respect to the four to seven amino acid segment of the candidate peptide that corresponds to the amino acid sequence of any one of SEQ ID NOs:2-14. An anti-PSMA peptide as described herein also can be designed to provide additional sequences, such as, for example, the addition of added C-terminal or N-terminal amino acids that can, for example, facilitate purification by trapping on columns or use of antibodies. Such tags include, for example, histidine-rich tags that allow purification of peptides on nickel columns. Such gene modification techniques and suitable additional sequences are well known in the molecular biology arts. The in vivo therapeutic effect of the PSMA-targeted oncolytic Ad was analyzed in CWR22Rv1 (PSMA-positive) pancreatic cancer subcutaneous xenografts (FIG.2).5×109vp of STMG-Ad or Ad5 WT were injected intratumorally at one, three, and six weeks after mice were injected with CWR22Rv1 cells. Over time, the injected cells formed a subcutaneous, PSMA- positive tumor. The PSMA-targeted virus (STMG-Ad) exhibited significant tumor volume reduction relative to the untreated and Ad5 WT treated animals. Individual tumor growth curves are shown in FIG 3. To investigate replication and intratumoral spread of the virus, tumors infected as described herein were harvested, sectioned, and stained using immunohistochemistry to detect the virus structural protein, hexon, five days after infection. After treatment with STMG-Ad (PSMA-OAd), many cells in the CWR22Rv1 tumors expressed high levels of hexon protein, while there were no hexon-positive cells in non-infected specimens (FIG.7). The non-targeted virus, Ad5 WT, resulted in moderate level of hexon expression in CWR22Rv1 cells. The hexon immunostaining signal from cells infected with STMG-Ad was remarkably higher than cells infected with Ad5 WT (FIG.7). These data indicated the viral replication of PSMA-retargeted adenovirus correlates with the anti-tumor effect. These experiments confirmed the selectivity and potency of the oncolytic adenovirus with STMGTSH (SEQ ID NO:3) as a targeting motif against PSMA-positive tumors. To further interrogate whether the anti-CWR22Rv1 tumor activity of STMG-Ad could be attributed to PSMA-binding, experiments were carried out in plated cells. Mice were implanted with tumors formed from either CWR22Rv1 cells treated with short hairpin RNA (shRNA) to silence expression of PSMA or not treated with shRNA. Mice were then treated with STMG-Ad and tumor volumes were measured over the course of 16 weeks (FIG.1). PC3 cells (PSMA-negative) and CWR22Rv1 cells (PSMA-positive) were treated with STMG-Ad at a concentration of 10 vp / cell.5 days after infection, cells were harvested and virus copy number was measured using E4 qPCR as described herein. PC3 cells had a very low number of virus copies, while CWR22Rv1 cells had a relatively high number of virus copies (FIG.6A). In addition, STMG-Ad showed cytocidal activity on CWR22Rv1 cells infected with 100 vp / cell at Day 5. In contrast, STMG-Ad did not have cytocidal activity on PC3 cells infected with 100 vp / cell (FIG.6B). Thus, STMG-Ad has a stronger cytocidal effect on PSMA-positive CWR22Rv1 cells than PSMA-negative PC3 cells. DU145 cells (PSMA-negative) and CWR22Rv1 cells (PSMA-positive) were treated with STMG-Ad at a concentration of 1, 10, and 100 vp / cell. STMG-Ad showed cytocidal activity on CWR22Rv1 cells infected with more than 1 vp at Day 8. In contrast, STMG-Ad did not have cytocidal activity on DU145 cells infected with less than 100 vp / cell (FIG.7). Thus, STMG-Ad has a stronger cytocidal effect on PSMA-positive CWR22Rv1 cells than PSMA-negative UD145 cells (FIG.7). Multispecific Compounds An anti-PSMA peptide may be incorporated into a multispecific compound. As used herein, the terms “multispecific compound” and “multispecific protein” refer to a biologically active polypeptide that includes two or more binding domains, with or without a further effector molecule, covalently linked (e.g., fused) by recombinant, chemical, or other suitable method. For example, a binding domain can be linked to another binding domain through a peptide linker sequence. Alternatively, a peptide linker may be used to assist in the construction of the fusion molecule. As used herein, the term “operably linked” refers to a direct or indirect covalent linking between the domains of the multispecific compound. Thus, two domains that are operably linked may be directly covalently coupled to one another. Conversely, two operably linked domains may be connected by mutual covalent linking to an intervening moiety (e.g., a flanking sequence or linker). Two domains may be considered operably linked if, for example, they are separated by the third domain, with or without one or more intervening flanking sequences or linkers. Domains of a multispecific compound can be in assembled operable linkage with one another using one or more linkers. The term “linker” as used herein refers any bond, small molecule, peptide sequence, or other vehicle that physically links the domains. Linkers can be susceptible to or be substantially resistant to acid-induced cleavage, light-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, and disulfide bond cleavage at conditions under which the compound or the antibody remains active. Linkers are classified upon their chemical motifs, well known in the art, including disulfide groups, hydrazine, or peptides (cleavable), or thioester groups (non-cleavable). Linkers also include charged linkers, and hydrophilic forms thereof as known in the art. Suitable linker for linking domains of a multispecific anti-PSMA compound can include natural linkers, empirical linkers, or a combination of natural and empirical linkers. Natural linkers are derived from multi-domain proteins, which are naturally present between protein domains. Properties of natural linkers such as, for example, length, hydrophobicity, amino acid residues, and / or secondary structure can be exploited to confer desirable properties to a multi- domain compound that includes natural linkers connecting functional domains. The studies of linkers in natural multi-domain proteins have led to the generation of many empirical linkers with various sequences and conformations for the construction of recombinant fusion proteins. Empirical linkers can be classified in three types: flexible linkers, rigid linkers, and cleavable linkers. Flexible linkers can provide a certain degree of movement or interaction at the joined domains. Flexible linkers typically include small, non-polar (e.g., Gly) or polar (e.g., Ser or Thr) amino acids, which provide flexibility, and allow for mobility of the connected functional domains. Rigid linkers can successfully keep a fixed distance between domains to maintain their independent functions, which can provide efficient separation of the protein domains and / or sufficiently reduce interference between functional domains. Cleavable linkers can allow one to control release of functional domains in vivo. By taking advantage of unique in vivo processes, cleavable linkers can be cleaved under specific conditions such as the presence of reducing reagents or proteases. This type of linker can reduce steric hindrance, improve bioactivity, and / or achieve independent actions / metabolism of individual domains of recombinant fusion proteins after linker cleavage. In one exemplary application, an anti-PSMA polypeptide can be incorporated into a multispecific NK engager compound that includes, at a minimum, the anti-PSMA protein and an NK engager domain. Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system capable of immune surveillance. Like T cells, NK cells deliver a store of membrane penetrating and apoptosis-inducing granzyme and perforin granules. Unlike T cells, NK cells do not require antigen priming and recognize targets by engaging activating receptors in the absence of MHC recognition. NK cells express CD16, an activation receptor that binds to the Fc portion of IgG antibodies and is involved in antibody-dependent cell-mediated cytotoxicity (ADCC). NK cells are regulated by IL-15, which can induce increased antigen-dependent cytotoxicity, lymphokine- activated killer activity, and / or mediate interferon (IFN), tumor-necrosis factor (TNF) and / or granulocyte-macrophage colony-stimulating factor (GM-CSF) responses. IL-15 can also drive NK cell proliferation and survival, thus enhancing expansion and persistence of NK cells. All of these IL-15-activated functions contribute to improved cancer defense. Therapeutically, adoptive transfer of NK cells can, for example, induce remission in subjects with refractory acute myeloid leukemia (AML) when combined with lymphodepleting chemotherapy and IL-2 to stimulate survival and in vivo expansion of NK cells. This therapy can be limited by lack of antigen specificity and IL-2-mediated induction of regulatory T (Treg) cells that suppress NK cell proliferation and function. Generating a reagent that drives NK cell antigen specificity, expansion, and / or persistence, while bypassing the negative effects of Treg inhibition, can enhance NK-cell-based immunotherapies. In one aspect, therefore, this disclosure describes the design, construction, and use of a trispecific molecule that includes two domains capable of driving NK-cell-mediated killing of PSMA+tumor cells and an intramolecular NK activating domain capable of generating an NK cell self-sustaining signal. The trispecific molecule can drive NK cell proliferation and / or enhance NK-cell-driven cytotoxicity against, for example, PSMA+cancer cells or PSMA+cancer cell-derived cell lines. This disclosure describes, in one aspect, trispecific killer engager molecules that generally include a targeting domain that selectively targets PSMA, an NK cell engager domain (e.g., CD16, CD16+CD2, CD16+DNAM, NKp46, CD16+NKp46, NKG2D, NK2C), and an NK activating domains (e.g., IL-15, IL-12, IL-18, IL-21, or other NK cell enhancing cytokine, chemokine, and / or activating molecule), with each domain operably linked to the other domains. As used herein, the terms “selectively targets” and “selectively binds” refer to the ability to differentiate between two or more alternatives such as, for example, having differential affinity, to any degree, for a particular target. Particularly in the context of a trispecific compound, the term “operably linked” includes domains connected by mutual covalent linking to an intervening moiety (e.g., a flanking sequence, multiple flanking sequences, and / or another functional domain). Thus, two domains may be considered operably linked if, for example, they are separated by a third functional domain, with or without one or more intervening flanking sequences. The targeting domain can include any peptide that includes the anti-PSMA motif STMG (SEQ ID NO:2) or a PSMA-binding variant thereof. Exemplary anti-PSMA peptides are provided in SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14. The NK engaging domain can include any moiety that binds to and / or activates an NK cell and / or any moiety that blocks inhibition of an NK cell. In one or more embodiments, the NK engaging domain can include an antibody that selectively binds to a component of the surface of an NK cell. In other embodiments, the NK engaging domain can include a ligand or small molecule that selectively binds to a component of the surface of an NK cell. Thus, for brevity, reference to an antibody that selectively binds to a component of the surface of an NK cell includes any antibody fragment that exhibits the described binding character. Similarly, reference to a ligand that selectively binds to a component of the surface of an NK cell includes any fragment of the ligand that exhibits the described binding character. In one or more embodiments, the NK engaging domain can selectively bind to a receptor at least partially located at the surface of an NK cell. In certain embodiments, the NK engaging domain can serve a function of binding an NK cell and thereby bring the NK cell into spatial proximity with a target to which the targeting domain selectively binds. In certain embodiments, however, the NK engaging domain can selectively bind to a receptor that activates the NK cell and, therefore, also possess an activating function. Activation of the CD16 receptor can elicit antibody-dependent cell-mediated cytotoxicity. Thus, in certain embodiments, the NK engaging domain can include at least a portion of an anti-CD16 receptor antibody effective to selectively bind to the CD16 receptor. In other embodiments, the NK engaging domain may interrupt mechanisms that inhibit NK cells. In such embodiments, the NK engaging domain can include, for example, anti-PD1 / PDL1, anti-NKG2A, anti-TIGIT, anti-killer-immunoglobulin receptor (KIR), and / or any other inhibition blocking domain. One can design the NK engaging domain to possess a desired degree of NK selectivity and, therefore, a desired immune engaging character. For example, CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b). These receptors bind to the Fc portion of IgG antibodies that then activates the NK cell for antibody-dependent cell-mediated cytotoxicity. Anti-CD16 antibodies selectively bind to NK cells, but also can bind to neutrophils. Anti-CD16a antibodies selectively bind to NK cells, but do not bind to neutrophils. A trispecific killer engager compound that includes an NK engaging domain that includes an anti-CD16a antibody can bind to NK cells but not bind to neutrophils. Thus, in circumstances where one may want to engage NK cells but not engage neutrophils, one can design the NK engaging domain of the trispecific killer engager compound to include an anti-CD16a antibody. As used throughout this description, “antibody” refers generally an immunoglobulin or a fragment thereof and thus encompasses a monoclonal antibody, a fragment thereof (e.g., scFv, Fab, F(ab’)2, Fv, sdAb, or other modified form of an antibody, including a humanized form of an antibody or fragment thereof). Thus, for brevity, reference to an antibody that selectively binds to a target includes any antibody or antibody fragment that exhibits the described binding character. Thus, reference to an antibody that selectively binds to CD16 (or any other NK cell receptor) includes any antibody or antibody fragment that exhibits the described binding character. In one or more embodiments, the NK cell engaging domain can involve the use of a humanized CD16 engager derived from an animal nanobody. While an scFv has a heavy variable chain component and a light variable chain component joined by a linker, a nanobody consists of a single monomeric variable chain—i.e., a variable heavy chin or a variable light chain—that is capable of specifically engaging a target. A single domain antibody (sdAb) may be derived from an antibody of any suitable animal such as, for example, a camelid (e.g., a llama or camel) or a cartilaginous fish. A single domain antibody can provide superior physical stability, an ability to bind deep grooves, and increased production yields compared to larger antibody fragments. In one exemplary embodiment, an sdAb-based NK engager molecule can involve a humanized CD16 nanobody derived from a llama nanobody (GeneBank sequence EF561291; Behar et al., 2008. Protein Eng Des Sel.21(1):1-10), termed EF91. Upon confirming functionality of the molecule, the CDRs were cloned into a humanized camelid scaffold to humanize the CD16 engager (Vincke et al., 2009. J Biol Chem.284(5):3273-3284). The use of a humanized camelid sdAb in the NK engaging domain of a trispecific killer engager compound can increase drug yield, increase stability, and / or increase NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC) efficacy. While described herein in the context of various embodiments in which the NK engaging domain includes an anti-CD16 sdAb or anti-CD16 scFv, the NK engaging domain can include any antibody or other ligand that selectively binds to CD16. Moreover, the NK engaging domain can include an antibody or ligand that selectively binds to any NK cell receptor such as, for example, the cell cytotoxicity receptor 2B4, low affinity Fc receptor CD16, killer immunoglobulin like receptors (KIR), CD2, NKG2A, TIGIT, NKG2C, LIR-1, and / or DNAM-1. In one aspect, the immune cell is a T cell or a natural killer (NK) cell. In another aspect, the immune cell is an NK cell and the immune cell engaging domain includes a ligand or antibody that specifically binds to CD16. In some aspects, the antibody that specifically binds to CD16 includes a an scFv, a F(ab)2, a Fab, or a single domain antibody. In one or more embodiments, the NK engaging domain and the targeting domain can be linked using any one of several linkers known to those of ordinary skill in the art to link functional domains of multifunctional proteins. In another aspect, the multispecific anti-PSMA compound further includes an immune cell activating domain. In one or more embodiments, the immune cell can be an NK cell and the immune cell activating domain includes a NK activating cytokine or a functional portion thereof. The NK activating domain can include a “immune cell activating domain”, e.g., an amino acid sequence that activates NK cells, promotes sustaining NK cells, or otherwise promotes NK cell activity. For example, NK cells are responsive to a variety of cytokines including, but not limited to, IL-15, which is involved in NK cell homeostasis, proliferation, survival, activation, and / or development. IL-15 and IL-2 share several signaling components, including the IL-2 / IL- 15R^ (CD122) and the common gamma chain (CD132). Unlike IL-2, IL-15 does not stimulate Tregs, allowing for NK cell activation while bypassing Treg inhibition of the immune response. Besides promoting NK cell homeostasis and proliferation, IL-15 can rescue NK cell functional defects that can occur in the post-transplant setting. IL-15 also can stimulate CD8+T cell function, further enhancing its immunotherapeutic potential. In addition, based on pre-clinical studies, toxicity profiles of IL-15 may be more favorable than IL-2 at low doses. Therefore, the NK activating domain can be, or can be derived from, one or more cytokines that can activate and / or sustain NK cells. As used herein, the term “derived from” refers to an amino acid fragment of a cytokine (e.g., IL-15) that is sufficient to provide NK cell activating and / or sustaining activity. In embodiments that include more than one NK activating domain, the NK activating domains may be provided in series or in any other combination. Additionally, each cytokine-based NK activating domain can include either the full amino acid sequence of the cytokine or may be an amino acid fragment, independent of the nature of other NK activating domains included in the trispecific killer engager compound. Exemplary cytokines on which an NK activating domain may be based include, for example, IL-15, IL-18, IL-12, and IL-21. Thus, while described in detail herein in the context of an exemplary model embodiment in which the NK activating domain is derived from IL-15, a trispecific killer engager compound may be designed using an NK activating domain that is, or is derived from, any suitable cytokine. For brevity in this description, reference to an NK activating domain by identifying the cytokine on which it is based includes both the full amino acid sequence of the cytokine, any suitable amino acid fragment of the cytokine, and or a modified version of the cytokine that includes one or more amino acid substitutions. Thus, reference to an “IL-15” NK activating domain includes an NK activating domain that includes the full amino acid sequence of IL-15, an NK activating domain that includes a fragment of IL-15, a functional variant thereof, or an NK activating domain that includes an amino acid substitution compared to the wild-type IL-15 amino acid sequence (SEQ ID NO:15). For example, an NK activating domain can include a fragment of IL-15 that includes an N-to-D or an N-to-A amino acid substitution at position 72 of SEQ ID NO:15. Reference to position 72 of SEQ ID NO:15 merely refers to the location of the amino acid substitution regardless of the particular fragment of IL-15 that may be used as the NK activating domain. Thus, the NK activating domain can include a fragment of IL-15 other than the fragment reflected in SEQ ID NO:15 and that fragment can have an N-to-D or an N-to-A amino acid substitution at the position of the alternative IL-15 fragment that corresponds to position 72 of SEQ ID NO:15. In one or more embodiments, trispecific anti-PSMA compounds include domains linked by one or more linkers (e.g., a combination of different linkers) well known to those of ordinary skill in the art as suitable for linking functional domains of engineered proteins. Nucleic acid sequences encoding proteins with an anti-PSMA motif In another aspect, this disclosure describes an isolated nucleic acid sequence that encodes any embodiment of an anti-PSMA compound described herein. Given the amino acid sequence of any anti-PSMA polypeptide, or multispecific anti-PSMA compound that includes an anti- PSMA polypeptide, a person of ordinary skill in the art can determine the full scope of polynucleotides that encode that amino acid sequence using conventional, routine methods. As used herein, the term “nucleic acid” or “oligonucleotide” refers to polynucleotides such as deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Nucleic acids include but are not limited to genomic DNA, cDNA, mRNA, iRNA, miRNA, tRNA, ncRNA, rRNA, and recombinantly produced and chemically synthesized molecules such as aptamers, plasmids, anti- sense DNA strands, shRNA, ribozymes, nucleic acids conjugates, and oligonucleotides. A nucleic acid may be single-stranded, double-stranded, linear, or covalently circularly closed molecule. A nucleic acid can be isolated. The term “isolated nucleic acid” means, that the nucleic acid (i) was amplified in vitro, for example via polymerase chain reaction (PCR), (ii) was produced recombinantly by cloning, (iii) was purified, for example, by cleavage and separation by gel electrophoresis, (iv) was synthesized, for example, by chemical synthesis, or (vi) extracted from a sample. A nucleic acid might be introduced—i.e., transfected—into cells. When RNA is used to transfect cells, the RNA may be modified by stabilizing modifications, capping, or polyadenylation. As used herein “amplified DNA” or “PCR product” refers to an amplified fragment of DNA of defined size. Various techniques are available and well known in the art to detect PCR products. PCR product detection methods include, but are not restricted to, gel electrophoresis using agarose or polyacrylamide gel and adding ethidium bromide staining (a DNA intercalant), labeled probes (radioactive or non-radioactive labels, southern blotting), labeled deoxyribonucleotides (for the direct incorporation of radioactive or non-radioactive labels) or silver staining for the direct visualization of the amplified PCR products; restriction endonuclease digestion, that relies agarose or polyacrylamide gel or high-performance liquid chromatography (HPLC); dot blots, using the hybridization of the amplified DNA on specific labeled probes (radioactive or non-radioactive labels); high-pressure liquid chromatography using ultraviolet detection; electro-chemiluminescence coupled with voltage-initiated chemical reaction / photon detection; and direct sequencing using radioactive or fluorescently labeled deoxyribonucleotides for the determination of the precise order of nucleotides with a DNA fragment of interest, oligo ligation assay (OLA), PCR, qPCR, DNA sequencing, fluorescence, gel electrophoresis, magnetic beads, allele specific primer extension (ASPE) and / or direct hybridization. Generally, nucleic acid can be extracted, isolated, amplified, or analyzed by a variety of techniques well known to those of ordinary skill in the art. Examples of nucleic acid analysis include, but are not limited to, sequencing and DNA-protein interaction. Sequencing may be by any method known in the art. DNA sequencing techniques include classic dideoxy sequencing reactions (Sanger method) using labeled terminators or primers and gel separation in slab or capillary, and next generation sequencing methods such as sequencing by synthesis using reversibly terminated labeled nucleotides, pyrosequencing, 454 sequencing, Illumina / Solexa sequencing, allele specific hybridization to a library of labeled oligonucleotide probes, sequencing by synthesis using allele specific hybridization to a library of labeled clones that is followed by ligation, real time monitoring of the incorporation of labeled nucleotides during a polymerization step, polony sequencing, and SOLiD sequencing. Separated molecules may be sequenced by sequential or single extension reactions using polymerases or ligases as well as by single or sequential differential hybridizations with libraries of probes. Genetically engineered cells In another aspect, this disclosure describes a host cell including any of the isolated nucleic acid sequences and / or proteins described herein. A nucleic acid construct encoding a protein that includes an anti-PSMA peptide may be introduced into a host cell to be altered, thus allowing expression of the chimeric protein within the cell, thereby generating a genetically engineered cell. A variety of methods are known in the art and suitable for introduction of nucleic acid into a cell, including viral and non-viral mediated techniques. Examples of typical non-viral mediated techniques include, but are not limited to, electroporation, calcium phosphate mediated transfer, nucleofection, sonoporation, heat shock, magnetofection, liposome mediated transfer, microinjection, microprojectile mediated transfer (nanoparticles), cationic polymer mediated transfer (DEAE-dextran, polyethylenimine, polyethylene glycol (PEG) and the like) or cell fusion. Other methods of transfection include proprietary transfection reagents such as LIPOFECTAMINE (Thermo Fisher Scientific, Inc., Waltham, MA), HILYMAX (Dojindo Molecular Technologies, Inc., Rockville, MD), FUGENE (Promega Corp., Madison, WI), JETPEI (Polyplus Transfection, Illkirch, France), EFFECTENE (Qiagen, Hilden, Germany) and DreamFect (OZ Biosciences, Inc USA, San Diego, CA). The nucleic acid constructs described herein may be introduced into a host cell to be altered, thus allowing expression within the cell of the protein encoded by the nucleic acid. A variety of host cells are known in the art and suitable for protein expression. Examples of typical cell used for transfection and protein expression include, but are not limited to, a bacterial cell, a eukaryotic cell, a yeast cell, an insect cell, or a plant cell such as, for example, E. coli, Bacillus, Streptomyces, Pichia pastoris, Salmonella typhimurium, Drosophila S2, Spodoptera SJ9, CHO, COS (e.g., COS-7),3T3-F442A, HeLa, HUVEC, HUAEC, NIH 3T3, Jurkat, 293, 293H, or 293F. In some aspects, the host cell is a T cell, an NK cell, or a macrophage. Targeted therapeutics In another aspect, this disclosure describes a targeted therapeutic compound that includes a targeting domain and a therapeutic domain linked to the targeting domain. The targeting domain includes any embodiment of an anti-PSMA protein that includes an STMG peptide motif. In one or more embodiments, the targeted therapeutic compound can provide immunotherapy and, therefore, be a targeted immunotherapeutic compound. In one or more embodiments, the therapeutic domain can include a drug, a therapeutic radioisotope, a toxin, a cytokine, or a chemokine. As used herein, the term “drug” refers to any chemical substance, which, when administered to a living organism, produces a biological effect. A pharmaceutical drug is a chemical substance used to treat, cure, prevent, or diagnose a disease or to promote well-being. Drugs can be obtained through extraction from medicinal plants, or by organic synthesis. Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders. A “radioisotope” or “radionuclide” is an atom that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferred to one of its electrons to release it as a conversion electron; or used to create and emit a new particle (alpha particle or beta particle) from the nucleus. During those processes, the radionuclide is said to undergo radioactive decay. These emissions are considered ionizing radiation because they are powerful enough to liberate an electron from another atom. The radioactive decay can produce a stable nuclide or will sometimes produce a new unstable radionuclide that may undergo further decay. As used herein, the term “toxin” refers to a substance harmful to cells. Toxins can be small molecules, peptides, or proteins that are capable of causing disease or cell death on contact with, or absorption by, body tissues. Toxins vary greatly in their toxicity. Toxins are largely secondary metabolites, which are organic compounds that are not directly involved in an organism’s growth, development, or reproduction, instead often aiding the organism in matters of defense. In some applications, a toxin may be used therapeutically by targeting the effect of the toxin toward an undesirable cell or cells (e.g., tumor cells). Cytokines are a broad category of small proteins (~5–20 kDa) involved in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm, but are nevertheless involved in autocrine, paracrine, and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells such as macrophages, B lymphocytes, T lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Pharmaceutical compositions and formulations In a further aspect, this disclosure describes a pharmaceutical composition that includes any one of the anti-PSMA compounds described herein and a pharmaceutically acceptable carrier. An anti-PSMA compound (e.g., a multispecific compound or targeted therapeutic compound) may be formulated with a pharmaceutically acceptable carrier. As used herein, “carrier” includes any solvent, dispersion medium, vehicle, coating, diluent, antibacterial, and / or antifungal agent, isotonic agent, absorption delaying agent, buffer, carrier solution, suspension, colloid, and the like. The use of such media and / or agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients also can be incorporated into the compositions. As used herein, “pharmaceutically acceptable” refers to a material that is not biologically or otherwise undesirable, i.e., the material may be administered to an individual along with a trispecific killer engager compound without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained. An anti-PSMA compound may therefore be formulated into a pharmaceutical composition. The pharmaceutical composition may be formulated in a variety of forms adapted to a preferred route of administration. Thus, a composition can be administered via known routes including, for example, oral, parenteral (e.g., intradermal, transcutaneous, subcutaneous, intramuscular, intravenous, intraperitoneal, etc.), or topical (e.g., intranasal, intrapulmonary, intramammary, intravaginal, intrauterine, intradermal, transcutaneous, rectally, etc.). A pharmaceutical composition can be administered to a mucosal surface, such as by administration to, for example, the nasal or respiratory mucosa (e.g., by spray or aerosol). A composition also can be administered via a sustained or delayed release. Thus, an anti-PSMA compound may be provided in any suitable form including but not limited to a solution, a suspension, an emulsion, a spray, an aerosol, or any form of mixture. The composition may be delivered in formulation with any pharmaceutically acceptable excipient, carrier, or vehicle. For example, the formulation may be delivered in a conventional topical dosage form such as, for example, a cream, an ointment, an aerosol formulation, a non-aerosol spray, a gel, a lotion, and the like. The formulation may further include one or more additives including such as, for example, an adjuvant, a skin penetration enhancer, a colorant, a fragrance, a flavoring, a moisturizer, a thickener, and the like. A formulation may be conveniently presented in unit dosage form and may be prepared by methods well known in the art of pharmacy. Methods of preparing a composition with a pharmaceutically acceptable carrier include the step of bringing a multispecific compound or trispecific killer engager compound into association with a carrier that constitutes one or more accessory ingredients. In general, a formulation may be prepared by uniformly and / or intimately bringing the active molecule into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product into the desired formulations. Methods of treatment and methods of use In another aspect, this disclosure describes methods of treatment and methods of use that involve administering an anti-PSMA compound to a subject. As used herein, “treat” or variations thereof refer to reducing, limiting progression, ameliorating, or resolving, to any extent, the symptoms or signs related to a condition. As used herein, “ameliorate” refers to any reduction in the extent, severity, frequency, and / or likelihood of a symptom or clinical sign characteristic of a particular condition; “symptom” refers to any subjective evidence of disease or of a subject’s condition; and “sign” or “clinical sign” refers to an objective physical finding relating to a particular condition capable of being found by one other than the subject. A “treatment” may be therapeutic or prophylactic. “Therapeutic” and variations thereof refer to a treatment that ameliorates one or more existing symptoms or clinical signs associated with a condition. “Prophylactic” and variations thereof refer to a treatment that limits, to any extent, the development and / or appearance of a symptom or clinical sign of a condition. Generally, a “therapeutic” treatment is initiated after the condition manifests in a subject, while “prophylactic” treatment is initiated before a condition manifests in a subject. Thus, in certain embodiments, the method can involve prophylactic treatment of a subject at risk of developing a condition. “At risk” refers to a subject that may or may not actually possess the described risk. Thus, for example, a subject “at risk” for developing a specified condition is a subject that possesses one or more indicia of increased risk of having, or developing, the specified condition compared to individuals who lack the one or more indicia, regardless of the whether the subject manifests any symptom or clinical sign of having or developing the condition. Exemplary indicia of a condition can include, for example, genetic predisposition, ancestry, age, sex, geographical location, lifestyle, or medical history. Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence. Accordingly, an anti-PSMA compound may be administered before, during, or after the subject first exhibits a symptom or clinical sign of the condition. Treatment initiated before the subject first exhibits a symptom or clinical sign associated with the condition may result in decreasing the likelihood that the subject experiences clinical evidence of the condition compared to a subject to which the anti-PSMA compound is not administered, decreasing the severity of symptoms and / or clinical signs of the condition, and / or completely resolving the condition. Treatment initiated after the subject first exhibits a symptom or clinical sign associated with the condition may result in decreasing the severity of symptoms and / or clinical signs of the condition compared to a subject to which the composition is not administered, and / or completely resolving the condition. The amount of anti-PSMA compound administered can vary depending on various factors including, but not limited to, the specific anti-PSMA compound being used, the weight, physical condition, and / or age of the subject, and / or the route of administration. Thus, the absolute weight of anti-PSMA compound included in a given unit dosage form can vary widely, and depends upon factors such as the species, age, weight, and physical condition of the subject, and / or the method of administration. Accordingly, it is not practical to set forth generally the amount that constitutes an amount of anti-PSMA compound effective for all possible applications. Those of ordinary skill in the art, however, can readily determine the appropriate amount with due consideration of such factors. In one or more embodiments, the method can include administering sufficient anti-PSMA compound to provide a dose of, for example, from about 100 ng / kg to about 50 mg / kg to the subject, although in one or more embodiments the methods may be performed by administering the anti-PSMA compound in a dose outside this range. In some of these embodiments, the method includes administering sufficient the anti-PSMA compound to provide a dose of from about 10 µg / kg to about 5 mg / kg to the subject, for example, a dose of from about 100 μg / kg to about 1 mg / kg. In another aspect, this disclosure describes a method including administering to a subject an NK-engaging anti-PSMA multispecific compound in an amount effective to induce NK- mediated killing of a cell that expresses PSMA. The NK-engaging anti-PSMA multispecific compound generally includes an NK engaging domain operably linked to an anti-PSMA peptide. In another aspect, this disclosure describes a method for stimulating expansion of NK cells in vivo including administering to a subject an NK-engaging anti-PSMA multispecific compound in an amount effective to stimulate expansion on NK cells in the subject. The NK- engaging anti-PSMA multispecific compound generally includes an NK engaging domain operably linked to an anti-PSMA peptide. In another aspect, this disclosure describes methods of killing a target cell in a subject wherein the target cell expresses PSMA. Generally, the method includes administering to the subject an NK-engaging anti-PSMA multispecific compound in an amount effective to induce NK-mediated killing of target cells that express PSMA. The NK-engaging anti-PSMA multispecific compound generally includes an NK engaging domain operably linked to an anti- PSMA peptide. In some cases, the treatment can involve administering the anti-PSMA multispecific compound to a subject so that the NK-engaging anti-PSMA multispecific compound can stimulate endogenous NK cells in vivo. In some cases, the NK-engaging anti-PSMA multispecific compound can be used in vitro as an adjuvant to NK cell adoptive transfer therapy. The anti-PSMA compound can be any embodiment of anti-PSMA compound having a targeting domain that includes an anti-PSMA motif that includes STMG (SEQ ID NO:2) or a structurally similar variant thereof. In some cases, the target cell can include a tumor cell that expresses PSMA so that the method can involve treating cancer associated with the tumor cells that express PSMA. Thus, in one or more embodiments, the method can include ameliorating at least one symptom or clinical sign of the tumor. In embodiments in which the target cell includes a tumor cell, the method can further include surgically resecting the tumor and / or reducing the size of the tumor through chemical (e.g., chemotherapeutic) and / or radiation therapy. Exemplary tumors that may be treated include, but are not limited to, tumors associated with prostate cancer, salivary gland cancer, thyroid cancer, hepatocellular carcinoma, renal cell carcinoma, glioblastoma, breast cancer, and lung cancer (Lauri et al., 2022, J. Clin. Med.11:6590). Thus, in one or more embodiments, treating a subject includes a subject having, or at risk of having cancer. Generally, the method includes administering to the subject an effective amount of anti-PSMA compound having a targeting domain that includes and anti-PSMA peptide with an STMG motif and an NK engaging domain operably linked to the anti-PSMA peptide. As used herein, the term “cancer” refers to a group of diseases characterized by abnormal and uncontrolled cell proliferation starting at one site (primary site) with the potential to invade and to spread to other sites (secondary sites, metastases) which differentiates cancer (malignant tumor) from benign tumor. Virtually any organ can be affected, meaning more than 100 types of cancer can affect humans. Cancers can result from many causes including genetic predisposition, viral infection, exposure to ionizing radiation, exposure to an environmental pollutant, tobacco and / or alcohol use, obesity, poor diet, lack of physical activity, or any combination thereof. As used herein, “neoplasm” or “tumor” (and grammatical variations thereof) means new and abnormal growth of tissue, which may be benign or cancerous. In a related aspect, the neoplasm is indicative of a neoplastic disease or disorder, including but not limited, to various cancers. In one aspect, the anti-PSMA compound is administered prior to, simultaneously with, or following chemotherapy, surgical resection of a tumor, or radiation therapy. In one or more embodiments, an anti-PSMA compound may be administered, for example, from a single dose to multiple doses per week, although in one or more embodiments the method can be performed by administering an anti-PSMA compound at a frequency outside this range. In certain embodiments, an anti-PSMA compound may be administered from about once per month to about five times per week. In one or more embodiments, the doses indicated above, which are described in terms of the amount of anti-PSMA compound administered over a 24-hour period, are administered in a seven-day cycle of four days of treatment and three days of rest. In one or more embodiments, an anti-PSMA compound may be administered, for example, from a single dose to multiple cycles of treatment, although in one or more embodiments the method can be performed by administering an anti-PSMA compound for a duration outside this range. In one or more embodiments, the anti-PSMA compound may be administered for three weeks. In such embodiments, each week may be a treatment cycle such as the exemplary treatment cycle described in the preceding paragraph. In other embodiments, the anti-PSMA compound may be administered for a greater number of treatment cycles, without a gap between one set of treatment cycles and a subsequent set of treatment cycles. The gap between one set of treatment cycles and a subsequent set of treatment cycles may be a gap of one or more weeks, one or more months, or one or more years. In one or more embodiments, the method further includes administering one or more additional therapeutic agents. The one or more additional therapeutic agents may be administered before, after, and / or coincident to the administration of a multispecific compound or trispecific killer engager compound. A multispecific compound or trispecific killer engager compound and the additional therapeutic agents may be co-administered. As used herein, “co-administered” refers to two or more components of a combination administered so that the therapeutic or prophylactic effects of the combination can be greater than the therapeutic or prophylactic effects of either component administered alone. Two components may be co-administered simultaneously or sequentially. Simultaneously co-administered components may be provided in one or more pharmaceutical compositions. Sequential co-administration of two or more components includes cases in which the components are administered so that each component can be present at the treatment site at the same time. Alternatively, sequential co-administration of two components can include cases in which at least one component has been cleared from a treatment site, but at least one cellular effect of administering the component (e.g., cytokine production, activation of a certain cell population, etc.) persists at the treatment site until one or more additional components are administered to the treatment site. Thus, a co-administered combination can, in certain circumstances, include components that never exist in a chemical mixture with one another. In other embodiments, the multispecific compound or trispecific killer engager compound and the additional therapeutic agent may be administered as part of a mixture or cocktail. In some aspects, the administration of the multispecific compound or trispecific killer engager compound may allow for the effectiveness of a lower dosage of other therapeutic modalities when compared to the administration of the other therapeutic agent or agents alone, thereby decreasing the likelihood, severity, and / or extent of the toxicity observed when a higher dose of the other therapeutic agent or agents is administered. The term “chemotherapeutic agent” as used herein refers to any therapeutic agent used to treat cancer. Examples of chemotherapeutic agents include, but are not limited to, actinomycin, azacitidine, azathioprine, bleomycin, bortezomib, carboplatin, capecitabine, cisplatin, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, epothilone, etoposide, fluorouracil, gemcitabine, hydroxyurea, idarubicin, imatinib, irinotecan, mechlorethamine, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, teniposide, tioguanine, topotecan, valrubicin, vinblastine, vincristine, vindesine, vinorelbine, panitumamab, Erbitux™ (cetuximab), matuzumab, IMC-IIF 8, TheraCIM hR3, denosumab, Avastin™ (bevacizumab), Humira™ (adalimumab), Herceptin™ (trastuzumab), Remicade™ (infliximab), rituximab, Synagis™ (palivizumab), Mylotarg™ (gemtuzumab oxogamicin), Raptiva™ (efalizumab), Tysabri™ (natalizumab), Zenapax™ (dacliximab), NeutroSpec™ (Technetium (99mTc) fanolesomab), tocilizumab, ProstaScint™ (Indium-Ill labeled Capromab Pendetide), Bexxar™ (tositumomab), Zevalin™ (ibritumomab tiuxetan (IDEC-Y2B8) conjugated to yttrium 90), Xolair™ (omalizumab), MabThera™ (Rituximab), ReoPro™ (abciximab), MabCampath™ (alemtuzumab), Simulect™ (basiliximab), LeukoScan™ (sulesomab), CEA-Scan™ (arcitumomab), Verluma™ (nofetumomab), Panorex™ (Edrecolomab), alemtuzumab, CDP 870, natalizumab Gilotrif™ (afatinib), Lynparza™ (olaparib), Perjeta™ (pertuzumab), Otdivo™ (nivolumab), Bosulif™ (bosutinib), Cabometyx™ (cabozantinib), Ogivri™ (trastuzumab-dkst), Sutent™ (sunitinib malate), Adcetris™ (brentuximab vedotin), Alecensa™ (alectinib), Calquence™ (acalabrutinib), Yescarta™ (ciloleucel), Verzenio™ (abemaciclib), Keytruda™ (pembrolizumab), Aliqopa™ (copanlisib), Nerlynx™ (neratinib), Imfinzi™ (durvalumab), Darzalex™ (daratumumab), Tecentriq™ (atezolizumab), and Tarceva™ (erlotinib). Examples of immunotherapeutic agent include, but are not limited to, interleukins (Il-2, Il-7, Il-12), cytokines (Interferons, G-CSF, imiquimod), chemokines (CCL3, CCl26, CXCL7), immunomodulatory imide drugs (thalidomide and its analogues). In one or more embodiments, the chemotherapy is selected from the group consisting of altretamine, amsacrine, L-asparaginase, colaspase, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytophosphane, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fluorouracil, fludarabine, fotemustine, ganciclovir, gemcitabine, hydroxyurea, idarubicin, ifosfamaide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitoxantrone, mitomycin C, nimustine, oxaliplatin, paclitaxel, pemetrexed, procarbazine, raltitrexed, temozolomide, teniposide, tioguanine, thiotepa, topotecan, vinblastine, vincristine, vindesine, and vinorelbine. In one or more embodiments, the method can include administering an anti-PSMA compound and administering the at least one additional therapeutic agent, each in an amount so that the combination demonstrates therapeutic synergy. In one or more embodiments, the treatment method can include measuring the response to treatment after the combination of the anti-PSMA compound and the additional therapeutic agent are administered. Therapeutic synergy may be evidenced by an improved response to treatment with the combination of anti- PSMA compound and additional therapeutic agent compared to the response after administering either the anti-PSMA compound or the additional therapeutic agent alone. The term “subject” as used herein refers to any individual or subject to which the subject methods are performed. In many embodiments, the subject is human, although the subject may be any non-human animal. Suitable non-human animals include, but are limited to, a vertebrate such as a rodent (including a mouse, a rat, a hamster, or a guinea pig), a cat, a dog, a rabbit, a farm animal (including a cow, a horse, a goat, a sheep, a pig, a chicken, etc.), or a primate (including a monkey, a chimpanzee, an orangutan, or a gorilla). Additional PSMA-targeting applications In another aspect, this disclosure describes a chimeric antigen receptor compound that includes an anti-PSMA STMG peptide motif. Chimeric antigen receptors (CARs, also known as chimeric immunoreceptors, chimeric T cell receptors, or artificial T cell receptors) are receptor proteins that have been engineered to give T cells the new ability to target a specific protein. The receptors are chimeric because they combine both antigen binding and T cell activating functions into a single receptor. CAR-T cell therapy uses T cells engineered with CARs for cancer therapy. The premise of CAR-T immunotherapy is to modify T cells to recognize cancer cells to target and destroy the cancer cells more effectively. T cells are harvested from a donor (autologous or allogeneic), genetically altered, then the resulting CAR-T cells are infused into a subject to attack the subject’s tumor. CAR-T cells can be either derived from T cells in a subject’s own blood (autologous) or derived from the T cells of a donor (allogeneic). Once isolated from a person, these T cells are genetically engineered to express a specific CAR that programs the T cells to target an antigen that is present on the surface of a tumor. For safety, CAR-T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells. After CAR-T cells are infused into a subject, they act as a “living drug” against cancer cells. When the CAR-T cells contact their targeted antigen on a cell, CAR-T cells bind to the antigen, become activated, proliferate, and become cytotoxic. CAR-T cells destroy cells through several mechanisms including extensive stimulated cell proliferation, increasing the degree to which they are toxic to other living cells (cytotoxicity), and by inducing increased secretion of factors that can affect other cells (e.g., cytokines, interleukins, and / or growth factors). In a further aspect, this disclosure describes a targeted imaging compound that includes a targeting domain and an imaging domain linked to the targeting domain. The targeting domain includes any embodiment of anti-PSMA peptide that includes an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof. The imaging domain can include any moiety that can produce a detectable signal. Exemplary imaging moieties include, but are not limited to a colorimetric label, a fluorescent label, a radioactive label, a magnetic label, or an enzymatic label. In yet another aspect, this disclosure describes a capture assay device including any embodiment of anti-PSMA peptide described herein immobilized to a substrate. For example, an anti-PSMA peptide can be incorporated into cell and / or ligand capture technology such as, for example, an ELISA-based assay. A substrate to immobilize the anti-PSMA proteins can include, for example, a cell culture plate or dish, a glass slide, or any other support than can be used to perform an assay requiring an immobilized anti-PSMA protein. In the preceding description and following claims, the term “and / or” means one or all of the listed elements or a combination of any two or more of the listed elements; the terms “comprises,” “comprising,” and variations thereof are to be construed as open ended—i.e., additional elements or steps are optional and may or may not be present; unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably and mean one or more than one; and the recitations of numerical ranges by endpoints include all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.). As used herein, “have,” “has,” “having,” “include,” “includes,” “including,” “comprise,” “comprises,” “comprising” or the like are used in their open-ended inclusive sense, and generally mean “include, but not limited to,” “includes, but not limited to,” or “including, but not limited to.” Further, wherever embodiments are described herein with the language “have,” “has,” “having,” “include,” “includes,” “including,” “comprise,” “comprises,” “comprising” and the like, otherwise analogous embodiments described in terms of “consisting of” and / or “consisting essentially of” are also provided. The term “consisting of” means including, and limited to, that which follows the phrase “consisting of.” That is, “consisting of” indicates that the listed elements are required or mandatory, and that no other elements may be present. The term “consisting essentially of” indicates that any elements listed after the phrase are included, and that other elements than those listed may be included provided that those elements do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. As used herein, the word “exemplary” means to serve as an illustrative example and should not be construed as preferred or advantageous over other embodiments. As used herein, the terms “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the invention. In the preceding description, particular embodiments may be described in isolation for clarity. Reference throughout this specification to “one embodiment,” “an embodiment,” “certain embodiments,” “one or more embodiments,” or “some embodiments,” etc., means that a particular feature, configuration, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of such phrases in various places throughout this specification are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments. Thus, features described in the context of one embodiment may be combined with features described in the context of a different embodiment except where the features are necessarily mutually exclusive. In several places throughout the above description, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list. For any method disclosed herein that includes discrete steps, the steps may be performed in any feasible order. And, as appropriate, any combination of two or more steps may be performed simultaneously. EXAMPLES The present invention is illustrated by the following examples. It is to be understood that the particular examples, materials, amounts, and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein. Binding and replication assay One day after the cells were seeded (1×107cells / 6cm dish), the cells were infected with virus at 100 vp / cell. The dishes for binding assay were incubated at 4°C for two hours to allow viruses to bind to cells while preventing internalization of the virus into the cells, and DNA was isolated after extensive wash with PBS. For analyzing virus replication, the dishes were incubated at 37°C for five days. DNA isolation and qPCR for E4 genes were performed as described. Flow-cytometry Cultured cells (2×105) were dissociated with Dissociation Buffer (Sigma-Aldrich, St. Louis, MO). Fluorescent conjugated (5 µl (1:20 dilution), A mouse APC-anti-hPSMA monoclonal antibody [Clone: LNI-17], BioLegend, San Diego, CA) was added to the cells and incubated for one hour at 4 °C. The cells were then washed twice and analyzed on a flow cytometer (BD FACS CANTO II: BD Biosciences, Franklin Lakes, NJ). In vivo tumor reduction To analyze the anti-tumor effect in an in vivo model, 106CWR22Rv1 cells were inoculated subcutaneously into the flank of the female nude mice, and 5×109vp of either SMTG- Ad (with targeted fiber) or Ad5 WT (with wild type fiber) was intravenously injected three times (at Day0, Day3, and Day6) when the diameter reached 5-7 mm. The condition of the mice was monitored daily, and the tumor diameter was measured twice a week. The tumor volume was calculated as width2× length / 2. The animal experiments were performed in accordance with the institutionally-approved animal experimental protocol. Mice were sacrificed five or 10 days after infection. The tumor specimens were cut in half; the first half was quickly frozen and kept at -80 °C until used, and the second half was fixed with buffered formaldehyde for immunostaining. The DNA was purified from frozen tumor tissue using a commercial kit (DNEASY Blood and Tissue Kit, Qiagen, Valencia, CA), and the adenoviral DNA copy number of the E4 region was quantified by qPCR starting from 20 ng DNA. The expression of adenoviral hexon protein in the tumor was analyzed by immunostaining. All slides were scanned at 10× and 4× magnification using a Nikon ECLIPSE TS100 microscope (Nikon Corp., Tokyo, Japan). In vivo distribution of the systemically injected viruses 106CWR22Rv1 cells were injected subcutaneously into athymic nude mice to implant a seed tumor.5×109viral particles of either SMTG-Ad (with targeted fiber) or Ad5 WT (with wild type fiber) were intravenously injected into mice when the seed tumor reached a diameter of 5-7 mm. After two days, major organs and tumors were harvested. DNA was purified using a commercial kit (DNEASY Blood and Tissue Kit, Qiagen, Valencia, CA), and the adenoviral DNA copy number of the E4 region was quantified by qPCR starting from 20 ng DNA. Statistical analysis Statistical comparisons between two groups were evaluated by Student’s t-test. Continuous variables were compared by Mann-Whitney-U test. All P-values were 2-sided, and a value of P<0.05 was considered to indicate statistical significance. The complete disclosure of all patents, patent applications, and publications, and electronically available material (including, for instance, nucleotide sequence submissions in, e.g., GenBank and RefSeq, and amino acid sequence submissions in, e.g., SwissProt, PIR, PRF, PDB, and translations from annotated coding regions in GenBank and RefSeq) cited herein are incorporated by reference in their entirety. In the event that any inconsistency exists between the disclosure of the present application and the disclosure(s) of any document incorporated herein by reference, the disclosure of the present application shall govern. The foregoing detailed description and examples have been given for clarity of understanding only. No unnecessary limitations are to be understood therefrom. The invention is not limited to the exact details shown and described, for variations obvious to one skilled in the art will be included within the invention defined by the claims. Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless otherwise indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. All numerical values, however, inherently contain a range necessarily resulting from the standard deviation found in their respective testing measurements. All headings are for the convenience of the reader and should not be used to limit the meaning of the text that follows the heading, unless so specified. Sequence Listing Free Text SEQ ID NO:1 – Human PSMA sequence (UniProt: A4UU13) MTAGSSYPLF LAAYACTGCL AERLGWFIKS SNEATSITPK HNMKAFLDEL KAENIKKFLY NFTQIPHLAG TEQNFQLAKQ TQSQWKEFGL DSVELAHYDV LLSYPNKTHP NYISIINEDG NEIFNTSLFE PPPPGYENVS DIVPPFSAFS PQGMPEGDLV YVNYARTEDF FKLERDMKIN CSGKIVIARY GKVFRGNKVK NAQLAGAKGV ILYSDPADYF APGVKSYPDG WNLPGGGVQR GNILNLNGAG DPLTPGYPAN EYAYRRGIAE AVGLPSIPVH PIGYYDAQKL LEKMGGSAPP DSSWRGSLKV PYNVGPGFTG NFSTQKVKMH IHSTNEVTRI YNVIGTLRGA VEPDRYVILG GHRDSWVFGG IDPQSGAAVV HEIVRSFGTL KKEGWRPRRT ILFASWDAEE FGLLGSTEWA EENSRLLQER GVAYINADSS IEGNYTLRVD CAPLMYSLVH NLTKELKSPD EGFEGKSLYE SWTKKSPSPE FSGMPRISKL GSGNDFEVFF QRLGIASGRA RYTKNWETNK FSGYPLYHSV YETYELVEKF YDPMFKYHLT VAQVRGGMVF ELANSIVLPF DCRDYAVVLR KYADKIYSIS MKHPQEMKTY SVSFDSLFSA VKNFTEIASK FSERLQDFDK SNPIVLRMMN DQLMFLERAF IDPLGLPDRP FYRHVIYAPS SHNKYAGESF PGIYDALFDI ESKVDPSKAW GEVKRQIYVA AFTVQAAAET LSEVA SEQ ID NO:2 – STMG sequence STMG SEQ ID NO:3 – STMGTSH sequence STMGTSH SEQ ID NO:4 – STMGTPH sequence STMGTPH SEQ ID NO:5 – STMGTSR sequence STMGTSR SEQ ID NO:6 – STMGASH sequence STMGASH SEQ ID NO:7 – SNMGTSH sequence SNMGTSH SEQ ID NO:8 – NTMGTSH sequence NTMGTSH SEQ ID NO:9 – STMVTSH sequence STMVTSH SEQ ID NO:10 – GTMGTSH sequence GTMGTSH SEQ ID NO:11 – STMHASH sequence STMHASH SEQ ID NO:12 – Consensus sequence X1X2MX3X4X5X6X1:S or N or G X2:T or N X3:G or V or H X4:T or A X5:S or P X6:H or R SEQ ID NO:13 – Consensus sequence X1X2MX3TX4H X1:S or N X2:T or N X3:G or V X4:S or P SEQ ID NO:14 – Consensus sequence X1TMX2X3SX4X1:S or G X2:G or H X3:T or A X4:H or R SEQ ID NO:15 – IL-15 fragment NWVNVISDLK KIEDLIQSMH IDATLYTESD VHPSCKVTAM KCFLLELQVI SLESGDASIH DTVENLIILA NNSLSSNGNV TESGCKECEE LEEKNIKEFL QSFVHIVQMF INTS

Claims

What is claimed is:

1. An anti-PSMA peptide comprising an STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof.

2. A multispecific compound comprising: a targeting domain comprising an anti-PSMA polypeptide, the anti-PSMA polypeptide comprising STMG (SEQ ID NO:2) motif or a structurally similar PSMA-binding variant thereof; and an immune cell engaging domain operably linked to the targeting domain.

3. The multispecific compound of claim 2, wherein the immune cell is a T cell or a natural killer (NK) cell.

4. The multispecific compound of claim 3, wherein: the immune cell is an NK cell; and the immune cell engaging domain comprises a ligand or antibody that specifically binds to CD16.

5. The multispecific compound of claim 4, wherein the antibody that specifically binds to CD16 comprises an scFv, a F(ab)2, a Fab, or a single domain antibody (sdAb).

6. The multispecific compound of claim 3, wherein: the immune cell comprises an NK cell; and the multispecific compound further comprises an immune cell activating domain comprising a cytokine or a functional portion thereof.

7. The multispecific compound of claim 6, wherein the cytokine is IL-15 or a functional variant thereof.

8. The multispecific compound of claim 7, wherein the immune cell activating domain comprises: SEQ ID NO:15; or an N72D amino acid substitution or N72A amino acid substitution compared to SEQ ID NO:

15.

9. An isolated nucleic acid sequence encoding the multispecific compound of any one of claims 2-8.

10. A protein encoded by the nucleic acid sequences of claim 9.

11. A host cell comprising the isolated nucleic acid of claim 9.

12. The host cell of claim 11, wherein the cell is a T cell, an NK cell, or a macrophage.

13. A pharmaceutical composition comprising: the multispecific compound of any one of claims 2-8; and a pharmaceutically acceptable carrier.

14. A method comprising: administering to a subject a multispecific compound in an amount effective to induce natural killer (NK)-mediated killing of a cell, the multispecific compound comprising: a targeting domain comprising the anti-PSMA peptide of claim 2; and an NK engaging domain operably linked to the targeting domain.

15. The method of claim 14, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14.

16. The method of claim 15, wherein the multispecific compound further comprises an immune cell activating domain comprising an IL-15 or a functional portion thereof, operably linked to the NK engaging domain.

17. A method for stimulating expansion of natural killer (NK) cells in vivo comprising: administering to a subject an effective amount of multispecific compound comprising: a targeting domain comprising the anti-PSMA polypeptide of claim 2; and an NK engaging domain operably linked to the anti-PSMA polypeptide.

18. The method of claim 17, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

14.

19. The method of claim 17, wherein the multispecific compound further comprises an immune cell activating domain comprising an IL-15 or a functional portion thereof, operably linked to the NK engaging domain.

20. A method of treating a subject having, or at risk of having cancer comprising: administering to the subject an effective amount of multispecific compound comprising: a targeting domain comprising the anti-PSMA polypeptide of claim 2; and an NK engaging domain operably linked to the anti-PSMA polypeptide.

21. The method of claim 20, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

14.

22. The method of claim 20, wherein the multispecific compound further comprises an immune cell activating domain comprising an IL-15 or a functional portion thereof, operably linked to the NK engaging domain.

23. The method of any one of claims 20-22, wherein cancer cells express PSMA.

24. The method of claim 23, wherein the cancer comprises prostate cancer, salivary gland cancer, thyroid cancer, hepatocellular carcinoma, renal cell carcinoma, glioblastoma, breast cancer, or lung cancer.

25. The method of any one of claims 20-24, wherein the multispecific compound is administered prior to, simultaneously with, or following chemotherapy, surgical resection of a tumor, or radiation therapy.

26. The method of claim 25, wherein the chemotherapy comprises altretamine, amsacrine, L- asparaginase, colaspase, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytophosphane, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fluorouracil, fludarabine, fotemustine, ganciclovir, gemcitabine, hydroxyurea, idarubicin, ifosfamaide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitoxantrone, mitomycin C, nimustine, oxaliplatin, paclitaxel, pemetrexed, procarbazine, raltitrexed, temozolomide, teniposide, tioguanine, thiotepa, topotecan, vinblastine, vincristine, vindesine, or vinorelbine.

27. A chimeric antigen receptor compound comprising the anti-PSMA peptide of claim 2.

28. The chimeric antigen receptor compound of claim 27 comprising any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

14.

29. A targeted immunotherapy compound comprising: a targeting domain comprising the anti-PSMA peptide of claim 2; and an immunotherapeutic domain linked to the targeting domain.

30. The targeted immunotherapy compound of claim 29, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

14.

31. A targeted therapeutic compound comprising: a targeting domain comprising the anti-PSMA peptide of claim 2; and a therapeutic domain linked to the targeting domain.

32. The targeted therapeutic compound of claim 31, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

14.

33. The targeted therapeutic compound of claim 31 or claim 32, wherein the therapeutic domain comprises a drug, a therapeutic radioisotope, a toxin, a cytokine, or a chemokine.

34. A targeted imaging compound comprising: a targeting domain comprising the anti-PSMA peptide of claim 2; and an imaging domain linked to the targeting domain.

35. The targeted imaging compound of claim 34, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

14.

36. The targeted imaging compound of claim 34 or claim 35, wherein the imaging domain comprises a colorimetric label, a fluorescent label, a radioactive label, a magnetic label, or an enzymatic label.

37. A capture assay device comprising the anti-PSMA peptide of claim 2 immobilized to a substrate.

38. The capture assay device of claim 37, wherein the anti-PSMA peptide comprises any one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:14.

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