Combination treatment of prostate cancers with two bispecific antibodies

Abstract

The application describes the first-in-human study on a PSMAxCD28 bispecific antibody, particularly on using a PSMAxCD28 bispecific antibody as a combination partner with a CD3 targeting molecule, in particular a KLK2xCD3 bi-specific antibody, to provide enhanced antitumor efficacy with a deeper and more durable clinical response, as well as an opportunity for enhanced tumor specificity by engaging two distinct tumor-associated antigens (TAAs).

Description

[0001] Attorney Docket No: 065768.12628 / 163WO1 - JBI6846 Combination Treatment of Prostate Cancers with Two Bispecific Antibodies FIELD OF THE INVENTION Disclosed are methods of treating prostate cancers and therapeutics to potentiate T-cell activation. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY This application contains a sequence listing, which is submitted electronically. The information contained in the electronic sequence listing (Sequence listing_065768.12208.xml; size: 47 KB; and date of creation: October 10, 2023) is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION Prostate cancer (PC) is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males, accounting for 14% (903,500) of the total new cancer cases and 6% (258,400) of the total cancer deaths in males worldwide. Historically, androgen depletion therapy (ADT) has been the standard of care for patients with metastatic prostate cancer. However, in the advanced form of prostate cancer, it becomes metastatic and spreads beyond the prostate to other parts of the body. With metastatic Castration-Resistant Prostate Cancer (mCRPC), hormone therapy no longer stops cancer growth. End stage PC (castration- resistant prostate cancer) currently has no curative treatment option. Antibody-based therapeutics have been used successfully to treat a variety of diseases, including cancer. One particular approach is to engineer a bispecific antibody with a first antigen binding domain that engages CD3 and a second antigen binding domain that engages an antigen associated with or upregulated on cancer cells so that the bispecific antibody redirects CD3+T cells to destroy the cancer cells. Bispecific antibodies that bind specifically to kallikrein related peptidase 2 (KLK2, hK2) and CD3 (KLK2xCD3 bi-specific antibodies) and uses thereof for treating cancer have been described. See, e.g., WO2021019389. However, tumor-infiltrating lymphocytes (TILs) may lose their cytotoxic ability over time due to upregulation of inhibitory immune checkpoints. While checkpoint blockade has demonstrated increased clinical response rates relative to other treatment options, many patients may still fail to achieve a response to checkpoint blockade. Engagement of costimulatory receptors on TILs could provide a positive signal capable of overcoming negative signals of immune checkpoints. Preclinical and clinical studies of agonistic costimulatory receptor antibodies have demonstrated that agonism of costimulatory receptors can result in improved anti-tumor responses, activating T cells to attack tumor cells. It is important for cancer therapy to enhance anti-tumor activity by specifically destroying tumor cells while minimizing peripheral toxicity. In this context, it is crucial that only T cells in the presence of the target tumor cells are provided a costimulatory signal. Nondiscriminatory stimulation of T cells may lead to off-tumor, on-target toxicity. Additionally, the tumor microenvironment, such as that in mCRPC, may lack a sufficient immune presence to allow for efficient immune-mediated cytotoxicity. In these so called “cold” tumors, T-cell redirection may be a particularly important approach to enhance immunoreactivity. There remains a need for novel immune response enhancing therapies for the treatment of prostate cancer, particularly advanced prostate cancer, particularly mCRPC. SUMMARY OF THE INVENTION The application describes the first-in-human study on a PSMAxCD28 bispecific antibody, particularly on using a PSMAxCD28 bispecific antibody as a combination partner with a CD3 targeting molecule, in particular a KLK2xCD3 bi-specific antibody, to provide enhanced antitumor efficacy with a deeper and more durable clinical response, as well as an opportunity for enhanced tumor specificity by engaging two distinct tumor-associated antigens (TAAs). Accordingly, in one general aspect, the invention provides a method of treating prostate cancer in a human subject in need thereof, wherein an isolated anti-hK2 / anti-CD3 bispecific antibody and an isolated anti-PSMA / anti-CD28 bispecific antibody are both administered to the human subject, and wherein the method comprises: (1) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, and (2) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 3, 4.5, 15, 30, 45 or 90 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration, of the isolated anti-PSMA / anti-CD28 bispecific antibody, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and wherein the first antigen binding domain comprises a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and wherein the third antigen binding domain comprises a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41, preferably wherein administering the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody provides a reduction in serum Prostate Specific Antigen (PSA), preferably an improved serum PSA reduction compared to administering the isolated anti-hK2 / anti-CD3 bispecific antibody at the same dose as the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody but without administering the anti-PSMA / anti-CD28 bispecific antibody, without triggering a cytokine release syndrome (CRS) of grade 3 or higher according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. According to embodiments of the application, each of the isolated anti-hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody can be administered subcutaneously, preferably by subcutaneous injection, or intravenously. The total quantity of the combination dose for each of the antibodies can be administered in one or more injections or shots as might be required. For example, one or more subcutaneous injection shots can be performed simultaneously or successively on the same day, as might be required, to administer the total quantity of the (or each) combination dose. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every 1 to 6 weeks, such as once every 1, 2, 3, 4, 5, or 6 weeks, and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific is administered once every 1 to 6 weeks, such as once every 1, 2, 3, 4, 5, or 6 weeks. In one embodiment, the invention provides a method of treating prostate cancer in a human subject in need thereof, comprising: (1) administering to the subject a combination dose of 400 mg or 200 mg, preferably 400 mg, per administration of an isolated anti-hK2 / anti-CD3 bispecific antibody of the application once every 3 weeks, and (2) administering to the subject a combination dose of 1.5, 4.5, 15, 45 or 90 mg per administration of an isolated anti-PSMA / anti-CD28 bispecific antibody of the application once every 3 weeks, wherein the administering of step (1) and the administering of step (2) are conducted on the same day, preferably the administering of step (2) is conduced within 1 hour after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or of each combination dose). In one embodiment, the invention provides a method of treating prostate cancer in a human subject in need thereof, comprising: (1) administering to the subject a combination dose of 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration of an isolated anti- hK2 / anti-CD3 bispecific antibody of the application once every 3 weeks, and (2) administering to the subject a combination dose of 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration of an isolated anti-PSMA / anti-CD28 bispecific antibody of the application once every 3 weeks, wherein the administering of step (1) and the administering of step (2) are conducted on the same day, preferably the administering of step (2) is conduced within 1 hour after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. In certain embodiments, a method of the application further comprises administering to the subject an initial treatment dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of the method of the application, preferably 5-10 days, such as 5, 6, 7, 8, 9, or 10 days, prior to the administering step (1) of the method of the application. In certain embodiments, the subject is administered an initial treatment dose of the same dose level as the combination dose, such as 200 mg or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering the combination dose, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), and preferably wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the subject is administered an initial treatment dose of the same dose level as the combination dose, such as 75, 100, 150 or 300 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering the combination dose, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and preferably wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In certain embodiments, a method of the application further comprises administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the initial administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein the one or more step-up doses are not higher than the combination dose of this antibody. In certain embodiments, the subject is administered an initial treatment dose of the isolated anti-hK2 / anti-CD3 bispecific antibody 1 week prior to the administering of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and the subject is further administered one or more step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, wherein the step-up doses are not higher than the initial treatment dose of this antibody. In some embodiments, the prostate cancer is advanced prostate cancer. In some embodiments, the prostate cancer is metastatic prostate cancer. In some embodiments, the prostate cancer is metastatic castration-resistant prostate cancer (mCRPC). In certain embodiments, the prostate cancer is mCRPC with histologically confirmed adenocarcinoma of the prostate. In certain embodiments, the prostate cancer is mCRPC with a prostate adenocarcinoma that has small cell or neuroendocrine (NE) features. IN certain embodiments, the prostate cancer is mCRPC with a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma. In some embodiments, the subject has received at least one androgen receptor (AR)- targeted therapy, such as a treatment with abiraterone acetate plus prednisone, apalutamide, enzalutamide, or darolutamide; or at least one chemotherapy, such as a treatment with docetaxel; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the subject has received orchiectomy or medical castration; or has received androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the subject has not undergone orchiectomy, and the method further comprises administering to the subject a GnRH analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic, preferably before each administration of a combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In certain embodiments, the subject is administered at least one first additional therapeutic, prior to being administered with the combination dose of the anti-hK2 / anti-CD3 bispecific antibody, or at least prior to being administered with the initial combination dose of anti-hK2 / anti-CD3 bispecific antibody. In certain embodiments, the subject is administered at least one first additional therapeutic, prior to being administered with the combination dose of the anti-hK2 / anti-CD3 bispecific antibody, or at least prior to being administered with the initial combination dose of anti-hK2 / anti-CD3 bispecific antibody, wherein the at least one first additional therapeutic is a glucocorticosteroid, antihistamine, antipyretic, or any combination thereof. In certain embodiments, the glucocorticosteroid is dexamethasone, beclomethasone, betamethasone, budesonide, cortisone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone, preferably dexamethasone. In certain embodiments, the antihistamine is diphenhydramine, brompheniramine, chlorpheniramine, clemastine, cypro.heptadine, dexchlorpheniramine dimenhydrinate, doxylamine, hydroxyzine, phenindamine, azelastine, loratadine, cetirizine, desloratadine, or fexofenadine, preferably diphenhydramine. In certain embodiments, the antipyretic is acetaminophen, ibuprofen, naproxen, ketoprofen, and nimesulide, aspirin, choline salicylate, magnesium salicylate, sodium salicylate, or phenazone (antipyrine), preferably acetaminophen. In some embodiments, the subject is administered at least one second additional therapeutic, prior to, and optionally after, being administered with the combination dose of anti- hK2 / anti-CD3 bispecific antibody, or at least prior to, and optionally after, being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the subject is administered at least one second additional therapeutic, prior to, and optionally after, being administered with the combination dose of anti- hK2 / anti-CD3 bispecific antibody, or at least prior to, and optionally after, being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein the at least one second additional therapeutic is an H2-antagonist, a leukotriene inhibitor, an antiemetic, or any combination thereof. In some embodiments, the subject is a male subject. In some embodiments, the subject is at least 18 years old. In some embodiments of the application, one or more of the PCWG3 disease Criteria are improved in the subject once he / she has received the isolated anti-hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody, compared to prior to the administration of the two bispecific antibodies; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody. For example, the serum PSA level of the subject decreases, preferably decreases 50% or more, compared to prior to the administration of the two bispecific antibodies, without triggering a cytokine release syndrome (CRS) of grade 3 or higher according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. In another general aspect, the invention presents an isolated anti-hK2 / anti-CD3 bispecific antibody for use in the method of any of the foregoing embodiments. In a final general aspect, the invention presents an isolated anti-PSMA / anti-CD28 bispecific antibody for use in the method of any of the foregoing embodiments. Further aspects, features and advantages of the present invention will be better appreciated upon a reading of the following detailed description of the invention and claims. BRIEF DESCRIPTION OF THE DRAWINGS The foregoing and other objects, aspects, features, and advantages of exemplary embodiments will become more apparent and may be better understood by referring to the following description taken in conjunction with the accompanying drawings. FIG.1 illustrates an example of the initial drug administration schedule to be evaluated. FIG.2 shows the effect of study PSMA x CD28 bispecific antibody + study hK2 x CD3 bispecific antibody combination treatment on SC VCaP PSMA+ / KLK2+ prostate xenografts in T-cell-humanized mice. FIG.3 shows the effect of study PSMA x CD28 bispecific antibody + study hK2 x CD3 bispecific antibody combination treatment on presence of tumor cells and CD3+T cells in PSMA+ / KLK2+VCaP tumors in T-cell-humanized mice (Study ONC2022-068). FIG.4 shows the in vitro cytotoxicity, T-cell activation, and cytokine release with combination treatments of study PSMA x CD28 bispecific antibody and fixed dose of study hK2 x CD3 bispecific antibody using PBMC’s from 5 healthy donors and VCaP target cells. FIG.5 shows the in vitro T-cell activation of the combination treatments of study PSMA x CD28 bispecific antibody with four different fixed doses of study hK2 x CD3 bispecific antibody using PBMCs and VCaP target cells at low E:T ratio. DETAILED DESCRIPTION OF THE INVENTION The disclosed methods may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures, which form a part of this disclosure. It is to be understood that the disclosed methods are not limited to the specific methods described and / or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed methods. All patents, published patent applications, and publications cited herein are incorporated by reference as if set forth fully herein. Various terms relating to aspects of the description are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definitions provided herein. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to “a cell” includes a combination of two or more cells, and the like. When a list is presented, unless stated otherwise, it is to be understood that each individual element of that list, and every combination of that list, is a separate embodiment. For example, a list of embodiments presented as “A, B, or C” is to be interpreted as including the embodiments, “A,” “B,” “C,” “A or B,” “A or C,” “B or C,” or “A, B, or C.” Unless otherwise stated, any numerical values, such as a concentration or a concentration range described herein, are to be understood as being modified in all instances by the term “about.” Thus, a numerical value typically includes ± 10% of the recited value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Likewise, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). As used herein, the use of a numerical range expressly includes all possible subranges, all individual numerical values within that range, including integers within such ranges and fractions of the values unless the context clearly indicates otherwise. Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the invention. The transitional terms “comprising.” “consisting essentially of,” and “consisting of” are intended to connote their generally accepted meanings in the patent vemacular; that is, (i) “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; (ii) “consisting of” excludes any element, step, or ingredient not specified in the claim; and (iii) “consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention. Embodiments described in terms of the phrase “comprising” (or its equivalents) also provide as embodiments those independently described in terms of “consisting of” and “consisting essentially of.” It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms, used herein when referring to a dimension or characteristic of a component of the preferred invention, indicate that the described dimension / characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one having ordinary skill in the art. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit. As used herein, the term “adverse event” (AE) refers to any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. According to embodiments of the invention, AEs are rated on a 3-point scale of increasing severity using the following definitions: mild (grade 1), referring to an AE that is easily tolerated by the subject, which causes minimal discomfort and does not interfere with everyday activities; moderate (grade 2), referring to an AE that is sufficiently discomforting to interfere with normal everyday activities and intervention may be needed; severe (grade 3), referring to an AE that prevents normal everyday activities, and treatment or other intervention is usually needed. A serious AE (SAE) can be any AE occurring at any dose that results in any of the following outcomes: death, where death is an outcome, not an event; life-threatening, referring to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which could hypothetically have caused death had it been more severe; in patient hospitalization, i.e., an unplanned, overnight hospitalization, or prolongation of an existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly / birth defect; important medical event (as deemed by the investigator) that may jeopardize the patients or may require medical or surgical intervention to prevent one of the other outcomes listed above (e.g., intensive treatment in an emergency room or at home for allergic bronchospasm or blood dyscrasias or convulsions that do not result in hospitalization). Hospitalization is official admission to a hospital. Hospitalization or prolongation of a hospitalization constitutes criteria for an AE to be serious; however, it is not in itself considered an SAE. In the absence of an AE, hospitalization or prolongation of hospitalization should not be reported as a SAE by the participating investigator. This can be the case, in the following situations: the hospitalization or prolongation of hospitalization is needed for a procedure required by the protocol; or the hospitalization or prolongation of hospitalization is a part of a routine procedure followed by the center (e.g., stent removal after surgery). This should be recorded in the study file. Hospitalization for elective treatment of a pre-existing condition that did not worsen during the study is not considered an AE. Complications that occur during hospitalization are AEs. If a complication prolongs hospitalization, or meets any of the other SAE criteria, then the event is an SAE. “Antibody-dependent cellular cytotoxicity”, “antibody-dependent cell-mediated cytotoxicity” or “ADCC” refers to the mechanism of inducing cell death that depends upon the interaction of antibody-coated target cells with effector cells possessing lytic activity, such as natural killer cells (NK), monocytes, macrophages and neutrophils via Fc gamma receptors (FcγR) expressed on effector cells. “Antibody-dependent cellular phagocytosis” or “ADCP” refers to the mechanism of elimination of antibody-coated target cells by internalization by phagocytic cells, such as macrophages or dendritic cells. “Antigen” refers to any molecule (e.g., protein, peptide, polysaccharide, glycoprotein, glycolipid, nucleic acid, portions thereof, or combinations thereof) capable of being bound by an antigen binding domain or a T-cell receptor capable of mediating an immune response. Exemplary immune responses include antibody production and activation of immune cells, such as T cells, B cells or NK cells. Antigens may be expressed by genes, synthetized, or purified from biological samples such as a tissue sample, a tumor sample, a cell or a fluid with other biological components, organisms, subunits of proteins / antigens, killed or inactivated whole cells or lysates. “Antigen binding fragment” or “antigen binding domain” refers to a portion of the protein that binds an antigen. Antigen binding fragments may be synthetic, enzymatically obtainable or genetically engineered polypeptides and include portions of an immunoglobulin that bind an antigen, such as the VH, the VL, the VH and the VL, Fab, Fab′, F(ab′)2, Fd and Fv fragments, domain antibodies (dAb) consisting of one VH domain or one VL domain, shark variable IgNAR domains, camelized VH domains, VHH domains, minimal recognition units consisting of the amino acid residues that mimic the CDRs of an antibody, such as FR3-CDR3-FR4 portions, the HCDR1, the HCDR2 and / or the HCDR3 and the LCDR1, the LCDR2 and / or the LCDR3, alternative scaffolds that bind an antigen, and multispecific proteins comprising the antigen binding fragments. Antigen binding fragments (such as VH and VL) may be linked together via a synthetic linker to form various types of single antibody designs where the VH / VL domains may pair intramolecularly, or intermolecularly in those cases when the VH and VL domains are expressed by separate single chains, to form a monovalent antigen binding domain, such as single chain Fv (scFv) or diabody. Antigen binding fragments may also be conjugated to other antibodies, proteins, antigen binding fragments or alternative scaffolds which may be monospecific or multispecific to engineer bispecific and multispecific proteins. “Antibodies” is meant in a broad sense and includes immunoglobulin molecules including monoclonal antibodies including murine, human, humanized and chimeric monoclonal antibodies, antigen binding fragments, multispecific antibodies, such as bispecific, trispecific, tetraspecific, dimeric, tetrameric or multimeric antibodies, single chain antibodies, domain antibodies and any other modified configuration of the immunoglobulin molecule that comprises an antigen binding site of the required specificity. “Full length antibodies” are comprised of two heavy chains (HC) and two light chains (LC) inter-connected by disulfide bonds as well as multimers thereof (e.g. IgM). Each heavy chain is comprised of a heavy chain variable region (VH) and a heavy chain constant region (comprised of domains CH1, hinge, CH2 and CH3). Each light chain is comprised of a light chain variable region (VL) and a light chain constant region (CL). The VH and the VL regions may be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with framework regions (FR). Each VH and VL is composed of three CDRs and four FR segments, arranged from amino-to-carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. Immunoglobulins may be assigned to five major classes, IgA, IgD, IgE, IgG and IgM, depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub-classified as the isotypes IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4. Antibody light chains of any vertebrate species may be assigned to one of two clearly distinct types, namely kappa (κ) and lambda (λ), based on the amino acid sequences of their constant domains. “Bispecific” refers to a molecule (such as an antibody) that specifically binds two distinct antigens or two distinct epitopes within the same antigen. The bispecific molecule may have cross- reactivity to other related antigens, for example to the same antigen from other species (homologs), such as human or monkey, for example Macaca cynomolgus (cynomolgus, cyno) or Pan troglodytes, or may bind an epitope that is shared between two or more distinct antigens. “Bispecific anti-hK2 / anti-CD3 antibody”, “hk2 / CD3 antibody”, “hk2xCD3 antibody,” “anti-hK2 / anti-CD3 protein,” and the like refer to an antibody that binds hk2 and CD3 and that comprises at least one binding domain specifically binding hK2 and at least one binding domain specifically binding CD3. The domains specifically binding hK2 and CD3 are typically VH / VL pairs. The bispecific anti-hk2xCD3 antibody may be monovalent in terms of its binding to either hk2 or CD3. “Cancer” refers to a broad group of various diseases characterized by the uncontrolled growth of abnormal cells in the body. Unregulated cell division and growth results in the formation of malignant tumors that invade neighboring tissues and may also metastasize to distant parts of the body through the lymphatic system or bloodstream. A “cancer” or “cancer tissue” can include a tumor. “Complement-dependent cytotoxicity” or “CDC”, refers to the mechanism of inducing cell death in which the Fc effector domain of a target-bound protein binds and activates complement component C1q which in turn activates the complement cascade leading to target cell death. Activation of complement may also result in deposition of complement components on the target cell surface that facilitate CDC by binding complement receptors (e.g., CR3) on leukocytes. “Complementarity determining regions” (CDR) are antibody regions that bind an antigen. There are three CDRs in the VH (HCDR1, HCDR2, HCDR3) and three CDRs in the VL (LCDR1, LCDR2, LCDR3). CDRs may be defined using various delineations such as Kabat (Wu et al. (1970) J Exp Med 132: 211-50; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), Chothia (Chothia et al. (1987) J Mol Biol 196: 901-17), IMGT (Lefranc et al. (2003) Dev Comp Immunol 27: 55- 77) and AbM (Martin and Thornton J Bmol Biol 263: 800-15, 1996). The correspondence between the various delineations and variable region numbering is described (see e.g., Lefranc et al. (2003) Dev Comp Immunol 27: 55-77; Honegger and Pluckthun, J Mol Biol (2001) 309:657-70; International ImMunoGeneTics (IMGT) database). Available programs such as abYsis by UCL Business PLC may be used to delineate CDRs. The term “CDR”, “HCDR1”, “HCDR2”, “HCDR3”, “LCDR”, “LCDR2” and “LCDR3” as used herein includes CDRs defined by any of the methods described supra, Kabat, Chothia, IMGT or AbM, unless otherwise explicitly stated in the specification. “CD3” refers to an antigen which is expressed on T cells as part of the multimolecular T cell receptor (TCR) complex and which consists of a homodimer or heterodimer formed from the association of two or four receptor chains: CD3 epsilon, CD3 delta, CD3 zeta and CD3 gamma. A human CD3 epsilon comprises the amino acid sequence of SEQ ID NO: 1. All references to proteins, polypeptides and protein fragments herein are intended to refer to the human version of the respective protein, polypeptide or protein fragment unless explicitly specified as being from a non-human species. Thus, “CD3” means human CD3 unless specified as being from a non-human species, e.g., “mouse CD3” “monkey CD3,” etc. Throughout the specification, “CD3-specific” or “specifically binds CD3” or “anti-CD3 antibody” refers to antibodies that bind specifically to a CD3-epsilon polypeptide, including antibodies that bind specifically to the CD3-epsilon extracellular domain (ECD). CD3-epsilon, together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha / beta and gamma / delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. CD3 is required for the immune response. The amino acid sequence of a human CD3 epsilon is shown in SEQ ID NO: 1. The amino acid sequence of a human CD3 epsilon extracellular domain is shown in SEQ ID NO:2. As used herein, the term “CD28” refers to Cluster of Differentiation 28, which is constitutively expressed on the surface of T cells and some natural killer cells. CD28 is also expressed on some B cells. CD28 is a type I transmembrane glycoprotein and is a member of the Immunoglobulin family by virtue of its single Ig variable-like extracellular domain. The term “CD28” includes any CD28 variant, isoform, and species homolog, which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding the polypeptide. Unless noted, preferably the CD28 is a human CD28. An exemplary human CD28 amino acid sequence is a human CD28 isoform 1 precursor sequence disclosed in NCBI Accession No. NP_006130. Another exemplary human CD28 amino acid sequence is a human CD28 isoform 2 precursor sequence disclosed in NCBI Accession No. NP_001230006, which is shown in SEQ ID NO: 46, where aa1-18 is the signal peptide. “Decrease,” “lower,” “lessen,” “reduce,” or “abate” refers generally to the ability of a test molecule to mediate a reduced response (i.e., downstream effect) when compared to the response mediated by a control or a vehicle. Exemplary responses are T cell expansion. T cell activation or T-cell mediated tumor cell killing or binding of a protein to its antigen or receptor, enhanced binding to a Fcγ or enhanced Fc effector functions such as enhanced ADCC, CDC and / or ADCP. Decrease may be a statistically significant difference in the measured response between the test molecule and the control (or the vehicle), or a decrease in the measured response, such as a decrease of about 1.1, 1.2, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or 30 fold or more, such as 500, 600, 700, 800, 900 or 1000 fold or more (including all integers and decimal points in between and above 1, e.g., 1.5, 1.6, 1.7, 1.8, etc.). “Enhance,” “promote,” “increase,” “expand” or “improve” refers generally to the ability of a test molecule to mediate a greater response (i.e., downstream effect) when compared to the response mediated by a control or a vehicle. Exemplary responses are T cell expansion, T cell activation or T-cell mediated tumor cell killing or binding of a protein to its antigen or receptor, enhanced binding to a Fcγ or enhanced Fc effector functions such as enhanced ADCC, CDC and / or ADCP. Enhance may be a statistically significant difference in the measured response between the test molecule and control (or vehicle), or an increase in the measured response, such as an increase of about 1.1, 1.2, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or 30 fold or more, such as 500, 600, 700, 800, 900 or 1000 fold or more (including all integers and decimal points in between and above 1, e.g., 1.5, 1.6, 1.7, 1.8, etc.). “Epitope” refers to a portion of an antigen to which an antibody specifically binds. Epitopes typically consist of chemically active (such as polar, non-polar or hydrophobic) surface groupings of moieties such as amino acids or polysaccharide side chains and may have specific three- dimensional structural characteristics, as well as specific charge characteristics. An epitope may be composed of contiguous and / or discontinuous amino acids that form a conformational spatial unit. For a discontinuous epitope, amino acids from differing portions of the linear sequence of the antigen come in close proximity in 3-dimensional space through the folding of the protein molecule. Antibody “epitope” depends on the methodology used to identify the epitope. “Express” and “expression” refers the to the well-known transcription and translation occurring in cells or in vitro. The expression product, e.g., the protein, is thus expressed by the cell or in vitro and may be an intracellular, extracellular or a transmembrane protein. “dAb” or “dAb fragment” refers to an antibody fragment composed of a VH domain (Ward et al., Nature 341:544546 (1989)). “Fab” or “Fab fragment” refers to an antibody fragment composed of VH, CH1, VL and CL domains. “F(ab′)2” or “F(ab′)2 fragment” refers to an antibody fragment containing two Fab fragments connected by a disulfide bridge in the hinge region. “Fd” or “Fd fragment” refers to an antibody fragment composed of VH and CH1 domains. “Fv” or “Fv fragment” refers to an antibody fragment composed of the VH and the VL domains from a single arm of the antibody. Fv fragments lack the constant regions of Fab (CH1 and CL) regions. The VH and VL in Fv fragments are held together by non-covalent interactions. “Fc” polypeptide” of a dimeric Fc refers to one of the two polypeptide forming the dimeric Fc domain. For example, an Fc polypeptide of a dimeric IgG FC comprises an IgG CH2 and an IgG CH3 constant domain sequence). “Full length antibody” is comprised of two heavy chains (HC) and two light chains (LC) inter-connected by disulfide bonds as well as multimers thereof (e.g. IgM). Each heavy chain is comprised of a heavy chain variable domain (VH) and a heavy chain constant domain, the heavy chain constant domain comprised of subdomains CH1, hinge, CH2 and CH3. Each light chain is comprised of a light chain variable domain (VL) and a light chain constant domain (CL). The VH and the VL may be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with framework regions (FR). Each VH and VL is composed of three CDRs and four FR segments, arranged from amino-to-carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. “Human antibody” refers to an antibody that is optimized to have minimal immune response when administered to a human subject. Variable regions of human antibody are derived from human immunoglobulin sequences. If human antibody contains a constant region or a portion of the constant region, the constant region is also derived from human immunoglobulin sequences. Human antibody comprises heavy and light chain variable regions that are “derived from” sequences of human origin if the variable regions of the human antibody are obtained from a system that uses human germline immunoglobulin or rearranged immunoglobulin genes. Such exemplary systems are human immunoglobulin gene libraries displayed on phage, and transgenic non-human animals such as mice or rats carrying human immunoglobulin loci. “Human antibody” typically contains amino acid differences when compared to the immunoglobulins expressed in humans due to differences between the systems used to obtain the human antibody and human immunoglobulin loci, introduction of somatic mutations or intentional introduction of substitutions into the frameworks or CDRs, or both. Typically, “human antibody” is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical in amino acid sequence to an amino acid sequence encoded by human germline immunoglobulin or rearranged immunoglobulin genes. In some cases, “human antibody” may contain consensus framework sequences derived from human framework sequence analyses, for example as described in Knappik et al., (2000) J Mol Biol 296:57-86, or a synthetic HCDR3 incorporated into human immunoglobulin gene libraries displayed on phage, for example as described in Shi et al., (2010) J Mol Biol 397:385-96, and in Int. Patent Publ. No. WO2009 / 085462. Antibodies in which at least one CDR is derived from a non-human species are not included in the definition of “human antibody”. “Humanized antibody” refers to an antibody in which at least one CDR is derived from non-human species and at least one framework is derived from human immunoglobulin sequences. Humanized antibody may include substitutions in the frameworks so that the frameworks may not be exact copies of expressed human immunoglobulin or human immunoglobulin germline gene sequences. “In combination with” means that two or more therapeutic agents are be administered to a subject together in a mixture, concurrently as single agents or sequentially as single agents in any order. “Isolated” refers to a homogenous population of molecules (such as synthetic polynucleotides or polypeptides) which have been substantially separated and / or purified away from other components of the system the molecules are produced in, such as a recombinant cell, as well as a protein that has been subjected to at least one purification or isolation step. “Isolated” refers to a molecule that is substantially free of other cellular material and / or chemicals and encompasses molecules that are isolated to a higher purity, such as to 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% purity. “Kallikrein related peptidase 2” or “KLK2” or “hK2” refers to a human protein which is also called kallikrein-2, grandular kallikrein 2, or HK2. hK2 is produced as a preproprotein and cleaved during proteolysis to generate active protease. All hK2 isoforms and variants are encompassed in “hK2”. The amino acid sequences of various isoforms are retrievable from public sources, such as GenBank accession numbers NP_005542.1, NP_001002231.1 and NP_001243009. The amino acid sequence of a full length hK2 is shown in SEQ ID NO: 3. The sequence includes the signal peptide (residues 1-18) and the pro-peptide region (residues 19-24). “Monoclonal antibody” refers to an antibody obtained from a substantially homogenous population of antibody molecules, i.e., the individual antibodies comprising the population are identical except for possible well-known alterations such as removal of C-terminal lysine from the antibody heavy chain or post-translational modifications such as amino acid isomerization or deamidation, methionine oxidation or asparagine or glutamine deamidation. Monoclonal antibodies typically bind one antigenic epitope. A bispecific monoclonal antibody binds two distinct antigenic epitopes. Monoclonal antibodies may have heterogeneous glycosylation within the antibody population. Monoclonal antibody may be monospecific or multispecific such as bispecific, monovalent, bivalent or multivalent. “Multispecific” refers to a molecule, such as an antibody that specifically binds two or more distinct antigens or two or more distinct epitopes within the same antigen. Multispecific molecule may have cross-reactivity to other related antigens, for example to the same antigen from other species (homologs), such as human or monkey, for example Macaca fascicularis (cynomolgus, cyno) or Pan troglodytes, or may bind an epitope that is shared between two or more distinct antigens. “Operatively linked” and similar phrases, when used in reference to nucleic acids or amino acids, refers to the operational linkage of nucleic acid sequences or amino acid sequence, respectively, placed in functional relationships with each other. For example, an operatively linked promoter, enhancer elements, open reading frame, 5′ and 3′ UTR, and terminator sequences result in the accurate production of a nucleic acid molecule (e.g., RNA) and in some instances to the production of a polypeptide (i.e., expression of the open reading frame). Operatively linked peptide refers to a peptide in which the functional domains of the peptide are placed with appropriate distance from each other to impart the intended function of each domain. The term “paratope” refers to the area or region of an antibody molecule which is involved in binding of an antigen and comprise residues that interact with an antigen. A paratope may composed of continuous and / or discontinuous amino acids that form a conformational spatial unit. The paratope for a given antibody can be defined and characterized at different levels of details using a variety of experimental and computational methods. The experimental methods include hydrogen / deuterium exchange mass spectrometry (HX-MS). The paratope will be defined differently depending on the mapping method employed. “Pharmaceutical combination” refers to a combination of two or more active ingredients administered either together or separately. “Pharmaceutical composition” refers to a composition that results from combining an active ingredient and a pharmaceutically acceptable carrier. “Pharmaceutically acceptable carrier” or “excipient” refers to an ingredient in a pharmaceutical composition, other than the active ingredient, which is nontoxic to a subject. Exemplary pharmaceutically acceptable carriers are a buffer, stabilizer or preservative. “Prevent,” “preventing,” “prevention,” or “prophylaxis” of a disease or disorder means preventing that a disorder occurs in a subject. “Protein” or “polypeptide” are used interchangeably herein are refers to a molecule that comprises one or more polypeptides each comprised of at least two amino acid residues linked by a peptide bond. Protein may be a monomer, or may be protein complex of two or more subunits, the subunits being identical or distinct. Small polypeptides of less than 50 amino acids may be referred to as “peptides”. Protein may be a heterologous fusion protein, a glycoprotein, or a protein modified by post-translational modifications such as phosphorylation, acetylation, myristoylation, palmitoylation, glycosylation, oxidation, formylation, amidation, citrullination, polyglutamylation, ADP-ribosylation, pegylation or biotinylation. Protein may be recombinantly expressed. As used herein, the term “prostate-specific membrane antigen” or “PSMA” refers to a type II membrane protein expressed on certain cells. The term “PSMA” as used herein includes the protein referred as HGNC: 3788, Entrez Gene: 2346, Ensembl: ENSG00000086205, OMIM: 600934, and UniProtKB: Q04609. The term “PSMA” includes any PSMA variant, isoform, and species homolog, which is naturally expressed by cells (including prostate cells) or can be expressed on cells transfected with genes or cDNA encoding the polypeptide. In specific embodiments, the PSMA is a human PSMA. An exemplary sequence of a human PSMA is provided in NP_001014986.1, shown in SEQ ID NO: 45 herein. “Recombinant” refers to polynucleotides, polypeptides, vectors, viruses and other macromolecules that are prepared, expressed, created or isolated by recombinant means. “Relapsed” refers to the return of a disease or the signs and symptoms of a disease after a period of improvement after prior treatment with a therapeutic. “Refractory” refers to a disease that does not respond to a treatment. A refractory disease can be resistant to a treatment before or at the beginning of the treatment, or a refractory disease can become resistant during a treatment. “Single chain Fv” or “scFv” refers to a fusion protein comprising at least one antibody fragment comprising a light chain variable region (VL) and at least one antibody fragment comprising a heavy chain variable region (VH), wherein the VL and the VH are contiguously linked via a polypeptide linker, and capable of being expressed as a single chain polypeptide. Unless specified, as used herein, a scFv may have the VL and VH variable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may comprise VL-linker-VH or may comprise VH-linker-VL. “(scFv)2” or “tandem scFv” or “bis-scFv” fragments refers to a fusion protein comprising two light chain variable region (VL) and two heavy chain variable region (VH), wherein the two VL and the two VH regions are contiguously linked via polypeptide linkers, and capable of being expressed as a single chain polypeptide. The two VL and two VH regions fused by peptide linkers form a bivalent molecule VLA-linker-VHA-linker-VLB-linker-VHB to form two binding sites, capable of binding two different antigens or epitopes concurrently. “Specifically binds,” “specific binding,” “specifically binding” or “binds” refer to a proteinaceous molecule binding to an antigen or an epitope within the antigen with greater affinity than for other antigens. Typically, the proteinaceous molecule binds to the antigen or the epitope within the antigen with an equilibrium dissociation constant (KD) of about 1×10−7M or less, for example about 5×10−8M or less, about 1×10−8M or less, about 1×10−9M or less, about 1×10−10M or less, about 1×10−11M or less, or about 1×10−12M or less, typically with the KD that is at least one hundred fold less than its KD for binding to a non-specific antigen (e.g., BSA, casein). In the context of the prostate neoantigens described here, “specific binding” refers to binding of the proteinacous molecule to the prostate neoantigen without detectable binding to a wild-type protein the neoantigen is a variant of. “Subject” includes any human or nonhuman animal. “Nonhuman animal” includes all vertebrates, e.g., mammals and non-mammals, such as nonhuman primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc. The terms “subject” and “patient” can be used interchangeably herein. “Therapeutically effective amount” or “effective amount” used interchangeably herein, refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result. A therapeutically effective amount may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of a therapeutic or a combination of therapeutics to elicit a desired response in the individual. Example indicators of an effective therapeutic or combination of therapeutics that include, for example, improved wellbeing of the patient, reduction of a tumor burden, arrested or slowed growth of a tumor, and / or absence of metastasis of cancer cells to other locations in the body. An “effective amount” can be a “combination dose”, a dosage amount of a drug product to be used when the drug product is administered to a subject in combination with another drug product. “Treat,” “treating” or “treatment” of a disease or disorder such as cancer refers to accomplishing one or more of the following: reducing the severity and / or duration of the disorder, inhibiting worsening of symptoms characteristic of the disorder being treated, limiting or preventing recurrence of the disorder in subjects that have previously had the disorder, or limiting or preventing recurrence of symptoms in subjects that were previously symptomatic for the disorder. “Tumor cell” or a “cancer cell” refers to a cancerous, pre-cancerous or transformed cell, either in vivo, ex vivo, or in tissue culture, that has spontaneous or induced phenotypic changes. These changes do not necessarily involve the uptake of new genetic material. Although transformation may arise from infection with a transforming virus and incorporation of new genomic nucleic acid, uptake of exogenous nucleic acid or it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation / cancer is exemplified by morphological changes, immortalization of cells, aberrant growth control, foci formation, proliferation, malignancy, modulation of tumor specific marker levels, invasiveness, tumor growth in suitable animal hosts such as nude mice, and the like, in vitro, in vivo, and ex vivo. “Variant,” “mutant” or “altered” refers to a polypeptide or a polynucleotide that differs from a reference polypeptide or a reference polynucleotide by one or more modifications, for example one or more substitutions, insertions or deletions. Unless indicated otherwise, the numbering of amino acid residues in the antibody constant region throughout the specification is according to the EU index as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991), unless otherwise explicitly stated. In some embodiments, antibodies described herein can comprise mutations (e.g., amino acid substitutions, additions, and / or deletions) outside of the CDRs (e.g., in framework regions (FRs) or constant regions). An amino acid substitution, addition, and / or deletion can be a substitution, addition, and / or deletion of one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more). An amino acid substitution, addition, and / or deletion can be a substitution, addition, and / or deletion of eight or fewer, seven or fewer, six or fewer, five or fewer, four or fewer, three or fewer, or two or fewer single amino acids. In some embodiments, antibodies described herein may include amino acid substitutions, additions, and / or deletions in the constant regions (e.g., Fc region) of the antibody that, e.g., lead to decreased effector function, e.g., decreased complement-dependent cytolysis (CDC) antibody-dependent cell-mediated cytolysis (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and / or decreased B-cell killing. For many applications of therapeutic antibodies, Fc-mediated effector functions are not part of the mechanism of action. These Fc-mediated effector functions can be detrimental and potentially pose a safety risk by causing off-mechanism toxicity. Modifying effector functions can be achieved by engineering the Fc regions to reduce their binding to FcgRs or the complement factors. The binding of IgG to the activating (FcgRI, FcgRIIa, FcgRIIIa and FcgRIIIb) and inhibitory (FcgRIIb) FcgRs or the first component of complement (C1q) depends on residues located in the hinge region and the CH2 domain. Mutations can be introduced in IgG1, IgG2 and IgG4 to reduce or silence Fc functionalities. Silencing mutations can include, but are not limited to IgG1 AA (F234A, L235A), IgG4 PAA (S228P, F234A, L235A), IgG2 AA (V234A, G237A), IgG1 FEA (L234F, L235E or D265A), IgG1 AAS (L234A, L235A, and D265S), or IgG1 FES (L234F / L235E / P331S). In some embodiments, the disclosed antibody or antigen-binding fragment thereof can contain the IgG1 AA (L234A, L235A) mutations. In some embodiments, the disclosed antibody or antigen-binding fragment thereof can contain IgG1 AAS (L234A, L235A, and D265S) mutations to eliminate effector function. The disclosed antibodies or antigen-binding fragments thereof can comprise an Fc region with one or more of the following properties: (a) reduced effector function when compared to the parent Fc; (b) reduced affinity to Fcg RI, Fcg RIIa, Fcg RIIb, Fcg RIIIb and / or Fcg RIIIa; (c) reduced affinity to FcgRI; (d) reduced affinity to FcgRIIa; I reduced affinity to FcgRIIb; (f) reduced affinity to Fcg RIIIb; or (g) reduced affinity to FcgRIIIa. In some embodiment, one or more mutations can be introduced into the CH3 domain of two heavy chains to favor formation of the heterodimer during co-transfection. “Heterodimerization” as used herein refers to an interaction of two heavy chains having non- identical CH3 amino acid sequences. “Heterodimer” as used herein refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences. The “knob-in-hole” strategy (see, e.g., PCT Publ. No. WO2006 / 028936) can be used to generate full length bispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a small side chain (hole) is introduced into a heavy chain of an antibody specifically binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody specifically binding a second antigen. After co- expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a “hole” with the heavy chain with a “knob.” Exemplary CH3 substitution pairs forming a knob and a hole are (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S and T366W / T366S_L368A_Y407V. For example, one heavy chain can feature a knob mutation: T366W while another heavy chain can feature the hole mutations: T366S, L368A, Y407V, and the knobs-into-holes mutations promote heterodimerization of the two heavy chains. Other strategies such as promoting heavy chain heterodimerization using electrostatic interactions by substituting positively charged residues at one CH3 surface and negatively charged residues at a second CH3 surface can be used, as described in US Pat. Publ. No. US2010 / 0015133; US Pat. Publ. No. US2009 / 0182127; US Pat. Publ. No. US2010 / 028637; or US Pat. Publ. No. US2011 / 0123532. In other strategies, heterodimerization can be promoted by the following substitutions (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): L351Y_F405AY407V / T394W, T3661_K392M_T394W / F405A_Y407V, T366L_K392M_T394W / F405A_Y407V, L351Y_Y407A / T366A_K409F, L351Y_Y407A / T366V K409F Y407A / T366A_K409F, or T350V_L351Y_F405A Y407V / T350V_T366L_K392L_T394W as described in U.S. Pat. Publ. No. US2012 / 0149876 or U.S. Pat. Publ. No. US2013 / 0195849. For example, L351Y, F405A and Y407V mutations can be introduced into one immunoglobulin constant region, and T394W can be introduced into another immunoglobulin constant region, and the interaction of the L351Y, F405A and Y407V mutations in the first Ig constant region and T394W mutation in the second Ig constant region promotes heterodimerization of the two immunoglobulin constant regions. In one general aspect, the application relates to a method of treating prostate cancer in a human subject in need thereof by administering to the human subject an effective amount of an isolated anti-hK2 / anti-CD3 bispecific antibody in combination with an effective amount of an isolated anti-PSMA / anti-CD28 bispecific antibody. As used herein, the term “in combination,” in the context of the administration of two or more therapies to a subject, refers to the use of more than one therapy. The use of the term “in combination” does not restrict the order in which therapies are administered to a subject. For example, a first therapy (e.g., a composition described herein) can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of a second therapy to a subject. In certain embodiments, in a method of treating prostate cancer in a human subject in need thereof, an isolated anti-hK2 / anti-CD3 bispecific antibody and an isolated anti-PSMA / anti-CD28 bispecific antibody are both administered to the human subject, and the method comprises: (1) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, and (2) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 3, 4.5, 15, 30, 45 or 90 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration, of the isolated anti-PSMA / anti-CD28 bispecific antibody, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and wherein the first antigen binding domain comprises a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and wherein the third antigen binding domain comprises a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41. Preferably, the administering of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody provides a reduction in serum Prostate Specific Antigen (PSA), preferably an improved serum PSA reduction compared to administering the isolated anti-hK2 / anti-CD3 bispecific antibody at the same dose as the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody but without administering the anti-PSMA / anti-CD28 bispecific antibody, without triggering a cytokine release syndrome (CRS) of grade 3 or higher according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Isolated anti-hK2 / anti-CD3 bispecific antibody and isolated anti-PSMA / anti-CD28 bispecific antibody useful for the invention, such as those described herein, can be obtained or prepared using methods known in the art in view of the present disclosure. In certain embodiments, an isolated anti-hK2 / anti-CD3 bispecific antibody useful for the method of the application is an anti-hK2 / anti-CD3 bispecific antibody described in US 2021 / 0040210, the content of which is incorporated herein by reference in its entirety. In certain embodiments, an isolated anti-PSMA / anti-CD28 bispecific antibody useful for the method of the application is an anti-PSMA / anti-CD28 bispecific antibody described in WO2023164510, the content of which is incorporated herein by reference in its entirety. In certain embodiment, an isolated anti-hK2 / anti-CD3 bispecific antibody useful for the method of the application comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and wherein the first antigen binding domain comprises a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11, and an isolated anti-PSMA / anti-CD28 bispecific antibody useful for the method of the application comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and wherein the third antigen binding domain comprises a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41. In some embodiments, the second antigen binding domain of the isolated anti-hK2 / anti- CD3 bispecific antibody comprises a second HCDR1, a second HCDR2, and a second HCDR3 of a second VH (VH2) of SEQ ID NO: 18 and a second LCDR1, a second LCDR2, and a second LCDR3 of a second VL (VL2) of SEQ ID NO: 19. In some embodiments, the first antigen binding domain comprises a first HCDR1, a first HCDR2, a first HCDR3, a first LCDR1, a first LCDR2 and a first LCDR3 of SEQ ID NOs: 4, 5, 6, 7, 8, and 9, respectively. In some embodiments, the second domain comprises the second HCDR1, the second HCDR2, the second HCDR3, the second LCDR1, the second LCDR2 and the second LCDR3 of SEQ ID NOs: 12, 13, 14, 15, 16, and 17, respectively. In some embodiments, the first antigen binding domain comprises a Fab, and the second antigen binding domain comprises a scFv. In some embodiments, the first antigen binding domain comprises a VH that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 10, and a VL that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 11; and the second antigen binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the first antigen binding domain comprises a Fab comprising a VH1 having the amino acid sequence of SEQ ID NO: 10 and a VL1 having the amino acid sequence of SEQ ID NO: 11; and wherein the second antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO: 20. In some embodiments, the first antigen binding domain is linked to a first immunoglobulin (Ig) constant region or a fragment of the first Ig constant region and / or the second antigen binding domain is linked to a second immunoglobulin (Ig) constant region or a fragment of the second Ig constant region, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype. In certain embodiments, the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1 isotype. In certain embodiments, the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprises at least one mutation that results in reduced binding of the anti-hK2 / anti-CD3 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat. In certain embodiments, the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof. In certain embodiments, the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprise one or more heterodimerization mutations to promote heterodimerization. In certain embodiments, the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V; or the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W. In certain embodiments, the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first heavy chain (HC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 21 and a first light chain (LC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 23, and a second heavy chain (HC2) that is at least 90%, 95% or 100% identical, to the amino acid sequence of SEQ ID NO: 24. In certain embodiments, the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a HC1 having the amino acid sequence of SEQ ID NO: 21, a LC1 having the amino acid sequence of SEQ ID NO: 23 and a HC2 having the amino acid sequence of SEQ ID NO: 24. In certain embodiments, the fourth antigen binding domain of the isolated anti- PSMA / anti-CD28 bispecific antibody comprises a fourth HCDR1, a fourth HCDR2, and a fourth HCDR3 of a fourth VH (VH4) of SEQ ID NO: 32, and a fourth LCDR1, a fourth LCDR2 and a fourth LCDR3 of a fourth VL (VL4) of SEQ ID NOs: 33, respectively. In certain embodiments, the third antigen binding domain comprises a third HCDR1, a third HCDR2, a third HCDR3, a third LCDR1, a third LCDR2, and a third LCDR3 of SEQ ID NO: 34, 35, 36, 37, 38, and 39, respectively. In certain embodiments, the fourth antigen binding domain comprises a fourth HCDR1, a fourth HCDR2, a fourth HCDR3, a fourth LCDR1, a fourth LCDR2, and a fourth LCDR3 of SEQ ID NO: 26, 27, 28, 29, 30, and 31, respectively. In some embodiments, the third antigen binding domain comprises a Fab, and the fourth antigen binding domain comprises an scFv, preferably the scFv comprises one or more cysteine substitutions. In certain embodiments, the third binding domain comprises a VH3 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 40, and a VL that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 41; and the fourth binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:47. In certain embodiments, the third binding domain comprises a VH3 having the amino acid sequence of SEQ ID NO: 40 and a VL3 having the amino acid sequence of SEQ ID NO: 41; and the second antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO: 47. In some embodiments, the third antigen binding domain is linked to a third immunoglobulin (Ig) constant region or a fragment of the third Ig constant region, and / or the fourth antigen binding domain is linked to a fourth immunoglobulin (Ig) constant region or a fragment of the fourth Ig constant region, wherein the third Ig constant region or the fragment of the third Ig constant region and / or the fourth Ig constant region or the fragment of the fourth Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype. In certain embodiments, one of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366S, L368A and Y407V, wherein the residues are numbered according to the EU index of Kabat. In certain embodiments, the third and fourth Ig constant regions or the fragments thereof each comprise one or more mutations that result in reduced binding of the anti-PSMA / anti-CD28 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat. In certain embodiments, the third or fourth Ig constant regions or the fragment thereof further comprises purification mutations H435R and Y436F, wherein the residues are numbered according to the EU index of Kabat. In certain embodiments, one of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / LT366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, wherein the residues are numbered according to the EU index of Kabat. In some embodiments, the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third heavy chain (HC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 44 and a third light chain (LC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 43, and a fourth heavy chain (HC4) that is at least 90%, at least 95% or 100% identical, to the amino acid sequence of SEQ ID NO: 42. In certain embodiments, the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a HC3 having the amino acid sequence of SEQ ID NO: 44, a LC3 having the amino acid sequence of SEQ ID NO: 43 and a HC4 having the amino acid sequence of SEQ ID NO: 42. According to embodiments of the application, each of the isolated anti-hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody can be administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). Each of the isolated anti-hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody can also be administered intravenously. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is of 0.5-2000 mg per administration, preferably 50-800 mg per administration, such as 400 mg or 200 mg per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is of 0.5-1800 mg per administration, preferably 50-800 mg per administration, such as 75, 100, 150 or 300 mg per administration, particularly 75, 150 or 300 mg per administration. In certain embodiments, the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody is administered subcutaneously, such as by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is of 0.5-2000 mg per administration, particularly 1.5-350 mg per administration, 1.5-300 mg per administration, 1.5- 200 mg per administration, or 1.5-100 mg per administration, such as 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration. In certain embodiments, the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously, preferably the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is of 0.5-1800 mg per administration, 0.5-350 mg per administration, 0.5-300 mg per administration, 0.5-200 mg per administration, or 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 3, 4.5, 15, 30, 45 or 90 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 50-800 mg, particularly 200-400 mg, such as 200 mg or 400 mg, preferably 400 mg per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 200 mg or 400 mg, preferably 400 mg per administration, wherein the isolated anti- hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration. In certain embodiments, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered at 200 mg or 400 mg, preferably 400 mg, per administration, and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered at 1.5, 4.5, 15, 45 or 90 mg per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered subcutaneously, preferably by subcutaneous injection, at 200 mg or 400 mg, preferably 400 mg, per administration, and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection, at 1.5, 4.5, 15, 45 or 90 mg per administration, wherein one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose of each of the isolated anti-hK2 / anti-CD3 bispecific and the isolated anti-PSMA / anti-CD28 bispecific antibodies. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), at 200 mg or 400 mg, preferably 400 mg, per administration, and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody is administered intravenously at 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, such as 1.5, 4.5, 15, 45 or 90 mg per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 200 mg or 400 mg, preferably 400 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5 mg per administration, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection, or the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 200 mg or 400 mg, preferably 400 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 4.5 mg per administration, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection, or the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 200 mg or 400 mg, preferably 400 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 15 mg per administration, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection, or the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 200 mg or 400 mg, preferably 400 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 45 mg per administration, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or the isolated anti-PSMA / anti- CD28 bispecific antibody is administered intravenously. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 200 mg or 400 mg, preferably 400 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 90 mg per administration, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or the isolated anti-PSMA / anti- CD28 bispecific antibody is administered intravenously. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. In certain embodiments, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration, wherein the isolated anti-PSMA / anti- CD28 bispecific antibody is administered intravenously or subcutaneously, such as by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered at 100 mg or 150 mg per administration, and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody is administered at 1.5, 4.5, 15, 45, or 90 mg per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered intravenously at 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, and the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection, at 1.5, 4.5, 15, 45 or 90 mg per administration, preferably by subcutaneous injection or infusion, more preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered intravenously at 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously, preferably at 1.5, 4.5, 15, 45 or 90 mg per administration. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5 mg per administration, preferably the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In some embodiment, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody at 1.5 mg per administration is administered subcutaneously, such as subcutaneous injection or infusion, preferably by subcutaneous injection. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 4.5 mg per administration, preferably the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In some embodiment, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody at 4.5 mg per administration is administered subcutaneously, such as subcutaneous injection or infusion, preferably by subcutaneous injection. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 15 mg per administration, preferably the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In some embodiment, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody at 15 mg per administration is administered subcutaneously, such as subcutaneous injection or infusion, preferably by subcutaneous injection. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 30 mg per administration, preferably the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In some embodiment, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody at 30 mg per administration is administered subcutaneously, such as subcutaneous injection or infusion, preferably by subcutaneous injection. In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 45 mg per administration, preferably the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In some embodiment, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody at 45 mg per administration is administered subcutaneously, such as subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 90 mg per administration, preferably the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In some embodiment, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration, preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously; and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody at 90 mg per administration is administered subcutaneously, such as subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every 1 to 6 weeks, such as once every 1, 2, 3, 4, 5, or 6 weeks, and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific is administered once every 1 to 6 weeks, such as once every 1, 2, 3, 4, 5, or 6 weeks. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every three weeks, and wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every three weeks. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every two weeks, and wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every two weeks. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every six weeks, and wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every six weeks. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every week, and wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every week. In some embodiments, the combination dose of the isolated anti-hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody are administered on the same day. Preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every three weeks, and wherein the combination dose of the isolated anti-hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti-hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 400 mg per administration. In some embodiments, the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti- PSMA / anti-CD28 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti-hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 400 mg per administration and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration. In certain embodiments, a method of the application further comprises administering to the subject an initial treatment dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) or the administering of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody of the method, preferably 5-10 days, such as 5, 6, 7, 8, 9, or 10 days, prior to the administering step (1) of the method. In some embodiments, the subject is administered an initial treatment dose of 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300 or 400 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the initial administration of the combination dose of the isolated anti- hK2 / anti-CD3 bispecific antibody, preferably 5-10 days, such as 5, 6, 7, 8, 9, or 10 days, prior to the initial administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiments, the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is of the same dose level as the combination dose of this antibody. In some embodiments, the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is lower than the combination dose of this antibody. In some embodiments, the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is 200 mg or 400 mg per administration, the combination dose of this antibody is 200 mg or 400 mg per administration, respectively, and wherein the isolated anti-hK2 / anti-CD3 antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or is administered intravenously. In some embodiments, the initial treatment dose of the isolated anti- hK2 / anti-CD3 antibody is 400 mg per administration, the combination dose of this antibody is 400 mg per administration, and wherein the isolated anti-hK2 / anti-CD3 antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and the isolated anti-PSMA / anti- CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or is administered intravenously. In some embodiments, the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is 75, 100, 150 or 300 mg per administration, the combination dose of this antibody is 75, 100, 150 or 300 mg per administration respectively, and wherein the isolated anti-hK2 / anti- CD3 antibody is administered intravenously; and the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or is administered intravenously. In some embodiments, the subject is administered one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the initial administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein the step-up doses are not higher than the combination dose and the isolated anti-hK2 / anti-CD3 bispecific antibody. In some embodiment, the step-up dose is the same dose level as the combination dose of this antibody. In some embodiment, the step-up dose is lower than the combination dose of this antibody. In some embodiments, the subject is administered one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administration of the initial treatment dose, wherein the step-up doses are not higher than the initial treatment dose. In some embodiment, the step-up dose is the same dose level as the initial treatment dose of this antibody. In some embodiment, the step-up dose is lower than the initial treatment dose of this antibody. In certain embodiments, the subject is administered a step-up dose of 30-70 mg per administration, such as 30, 40, 50, 60 or 70 mg per administration, preferably 50 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administration of the initial treatment dose or the combination does of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose or the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the subject is administered a step-up dose of 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administration of the initial treatment dose or the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose or the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. In certain embodiments, the subject is administered a first step-up dose and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the first step-up dose is prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the second step-up dose, and wherein the second step-up dose is prior to the administration of the initial treatment dose or the combination dose of the isolated anti- hK2 / anti-CD3 bispecific antibody, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose or the combination dose, wherein the first step-up dose is not higher than the second step-up dose, and the second step-up dose is not higher than the initial treatment dose or the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. In certain embodiments, the first step-up dose is 5-25 mg per administration, such as 5, 10, 15, 20 or 25 mg per administration, preferably 10 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, and the second step-up dose is of 30-70 mg per administration, such as 30, 40, 50, 60 or 70 mg, per administration, preferably 50 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion. In certain embodiments, the first step-up dose is 2-5 mg per administration, such as 2, 2.5, 3, 3.5, 4, 4.5 or 5 mg per administration, preferably 3.5 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and the second step-up dose is 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg, per administration, preferably 18 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and preferably the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. In certain embodiments, a method of the application further comprises administering to the subject one or more step-up doses of the isolated anti-PSMA / anti-CD28 bispecific antibody prior to the initial administration of the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody, wherein the step-up doses are not higher than the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody. In one embodiment, the invention provides a method of treating prostate cancer in a human subject in need thereof, comprising: (1) administering to the subject a combination dose of 50 mg – 800 mg, preferably 200 mg or 400 mg, per administration of an isolated anti-hK2 / anti-CD3 bispecific antibody of the application once every 1-6 weeks, preferably once every 3 weeks, and (2) administering to the subject a combination dose of 1.5, 4.5, 15, 45 or 90 mg per administration of an isolated anti-PSMA / anti-CD28 bispecific antibody of the application once every 1-6 weeks, preferably once every 3 weeks, wherein the administering of step (1) and the administering of step (2) are conducted on the same day, preferably the administering of step (2) is conduced within 1 hour after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein: (a) the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2 and a second antigen binding domain that binds specifically to CD3ε, wherein: i. the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; preferably, the first antigen binding domain comprises a VH1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 10 and a VL1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 11; more preferably, the first antigen binding domain comprises a HC1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 21 or 22 and a LC1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 23; ii. the second antigen binding domain comprises a second HCDR1, a second HCDR2, and a second HCDR3 of a second VH (VH2) of SEQ ID NO: 18 and a second LCDR1, a second LCDR2, and a second LCDR3 of a second VL (VL2) of SEQ ID NO: 19; preferably, the second antigen binding domain comprises a VH2 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 18 and a VL2 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 19; more preferably, the second antigen binding domain comprises an scFv that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 20; most preferably, the second antigen binding domain comprises a HC2 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 24; and (b) the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein: i. the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41; preferably, the third antigen binding domain comprises a VH3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 40 and a VL3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 41; more preferably, the third antigen binding domain comprises a HC3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 44 and a LC3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 43; and ii. the fourth antigen binding domain comprises a fourth HCDR1, a fourth HCDR2, and a fourth HCDR3 of a fourth VH (VH4) of SEQ ID NO: 32, and a fourth LCDR1, a fourth LCDR2 and a fourth LCDR3 of a fourth VL (VL4) of SEQ ID NOs: 33; preferably, the fourth antigen binding domain comprises a VH4 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 32 and a VL4 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 33; more preferably, the fourth antigen binding domain comprises a scFv that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 47; most preferably, the fourth antigen binding domain comprises a HC4 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 42. In certain embodiments, the subject is administered an initial treatment dose of 200 mg or 400 mg, particularly 400 mg, per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to administering the combination dose, such as the combination dose of 200 mg or 400 mg, particularly 400 mg, per administration, once every 3 weeks, wherein the isolated anti- hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), and the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose). In certain embodiments, the subject is administered an initial treatment dose of 400 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to being administered a combination dose, such as the combination dose of 400 mg per administration, once every 3 weeks, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection, and wherein the isolated anti-PSMA / anti- CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, or preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and wherein a step-up dose of 50 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose. In certain embodiments, the subject is administered an initial treatment dose of 400 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering of a combination dose, such as the combination dose of 400 mg per administration once every 3 weeks, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), and wherein the isolated anti- PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose); and wherein a first step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody are administered, wherein the first step-up dose is administered prior to the administration of the second step-up dose, preferably 3- 8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the second step-up dose, wherein the second step- up dose is prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, wherein the first step-up dose is of 10 mg per administration; and wherein the second step-up dose is of 50 mg per administration. In one embodiment, the invention provides a method of treating prostate cancer in a human subject in need thereof, comprising: (1) administering to the subject a combination dose of 50-800 mg, such as 75, 100, 150 or 300 mg, particularly 75, 150 or 300 mg, per administration of an isolated anti-hK2 / anti- CD3 bispecific antibody once every 1-6 weeks, preferably once every 3 weeks, and (2) administering to the subject a combination dose of 1.5, 4.5, 15, 30, 45, or 90 mg per administration, particularly 1.5, 4.5, 15, 45 or 90 mg per administration, of an isolated anti-PSMA / anti-CD28 bispecific antibody once every 1-6 weeks, wherein the administering of step (1) and the administering of step (2) are conducted on the same day, preferably the administering of step (2) is conduced within 1 hour after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein, (a) the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2 and a second antigen binding domain that binds specifically to CD3ε, wherein: i. the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; preferably, the first antigen binding domain comprises a VH1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 10 and a VL1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 11; more preferably, the first antigen binding domain comprises a HC1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 21 or 22 and a LC1 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 23; ii. the second antigen binding domain comprises a second HCDR1, a second HCDR2, and a second HCDR3 of a second VH (VH2) of SEQ ID NO: 18 and a second LCDR1, a second LCDR2, and a second LCDR3 of a second VL (VL2) of SEQ ID NO: 19; preferably, the second antigen binding domain comprises a VH2 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 18 and a VL2 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 19; more preferably, the second antigen binding domain comprises a scFv that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 20; most preferably, the second antigen binding domain comprises a HC2 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 24; and (b) the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein: i. the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41; preferably, the third antigen binding domain comprises a VH3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 40 and a VL3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 41; more preferably, the third antigen binding domain comprises a HC3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 44 and a LC3 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 43; and ii. the fourth antigen binding domain comprises a fourth HCDR1, a fourth HCDR2, and a fourth HCDR3 of a fourth VH (VH4) of SEQ ID NO: 32, and a fourth LCDR1, a fourth LCDR2 and a fourth LCDR3 of a fourth VL (VL4) of SEQ ID NOs: 33; preferably, the fourth antigen binding domain comprises a VH4 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 32 and a VL4 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 33; more preferably, the fourth antigen binding domain comprises a scFv that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 47; most preferably, the fourth antigen binding domain comprises a HC4 that is at least 90%, 95% or 100% identical to the amino acid sequence of SEQ ID NO: 42. In certain embodiments, the subject is administered an initial treatment dose of 75, 150 or 300 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering of the combination dose, such as the combination dose of 75, 150 or 300 mg per administration once every three weeks, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. In certain embodiments, the subject is administered an initial treatment dose of 75, 150 or 300 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering of the combination dose, such as the combination dose of 75, 150 or 300 mg per administration once every three weeks, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously; and wherein a step-up dose of 18 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered, preferably intravenously, 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose. In certain embodiments, the subject is administered an initial treatment dose of 75, 150 or 300 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering of the combination dose, such as the combination dose of 75, 150 or 300 mg per administration once every three weeks, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each combination dose), or the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously; and wherein a first step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of the isolated anti-hK2 / anti- CD3 bispecific antibody are administered, preferably intravenously, wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the second step-up dose, wherein the second step-up dose is administered prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, wherein the first step-up dose is 3.5 mg per administration; and wherein the second step-up dose is 18 mg per administration. In certain embodiments, the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the first antigen binding domain having the VH1 of SEQ ID NO: 10 and the VL1 of SEQ ID NO: 11, and the second antigen binding domain having the VH2 of SEQ ID NO: 18 and the VL2 of SEQ ID NO: 19. In certain embodiments, the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the third antigen binding domain having the VH3 of SEQ ID NO: 40 and the VL3 of SEQ ID NO: 41, and the fourth antigen binding domain having the VH4 of SEQ ID NO: 32 and the VL4 of SEQ ID NO: 33. In certain embodiments, the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the VH1 of SEQ ID NO: 10, the VL1 of SEQ ID NO: 11, the VH2 of SEQ ID NO: 18 and the VL2 of SEQ ID NO: 19, and the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the VH3 of SEQ ID NO: 40, the VL3 of SEQ ID NO: 41, the VH4 of SEQ ID NO: 32 and the VL4 of SEQ ID NO: 33. In certain embodiments, the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the first antigen binding domain having the HC1 of SEQ ID NO: 21 or 22 and the LC1 of SEQ ID NO: 23, and the second antigen binding domain having the HC2 of SEQ ID NO: 24. In certain embodiments, the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the HC3 of SEQ ID NO: 44 and the LC3 of SEQ ID NO: 43, and the fourth antigen binding domain having the HC4 of SEQ ID NO: 42. In certain embodiments, the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the HC1 of SEQ ID NO: 21 or 22, the LC1 of SEQ ID NO: 23, and the HC2 of SEQ ID NO: 24, and the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the HC3 of SEQ ID NO: 44, the LC3 of SEQ ID NO: 43, and the HC4 of SEQ ID NO: 42. The antibodies disclosed herein can be produced from a host cell. A host cell refers to a vehicle that includes the necessary cellular components, e.g., organelles, needed to express the polypeptides and constructs described herein from their corresponding nucleic acids. The nucleic acids may be included in nucleic acid vectors that can be introduced into the host cell by conventional techniques known in the art (e.g., transformation, transfection, electroporation, calcium phosphate precipitation, direct microinjection, infection, etc.). The choice of nucleic acid vectors depends in part on the host cells to be used. Generally, host cells are of either prokaryotic (e.g., bacterial) or eukaryotic (e.g., mammalian) origin. The antibodies disclosed herein can be administered in pharmaceutical compositions that include an effective amount of the antibody, and one or more pharmaceutically acceptable carriers or excipients, which can be formulated by methods known to those skilled in the art. Acceptable carriers and excipients in the pharmaceutical compositions are nontoxic to recipients at the dosages and concentrations employed. Acceptable carriers and excipients may include buffers, antioxidants, preservatives, polymers, amino acids, and carbohydrates. Pharmaceutical compositions can be administered parenterally in the form of an injectable formulation. Pharmaceutical compositions for injection can be formulated using a sterile solution or any pharmaceutically acceptable liquid as a vehicle. Pharmaceutically acceptable vehicles include, but are not limited to, sterile water, physiological saline, and cell culture media (e.g., Dulbecco’s Modified Eagle Medium (DMEM), α-Modified Eagles Medium (α-MEM), F-12 medium). Formulation methods are known in the art, see e.g., Banga (ed.) Therapeutic Peptides and Proteins: Formulation, Processing and Delivery Systems (2nded.) Taylor & Francis Group, CRC Press (2006). In some embodiments, antibodies useful for a method of the application can be packaged in one or more kits, which can optionally contain instructions for use. In some embodiments, a subject treated by a method of the application meets all of the following inclusion criteria: (1) Metastatic castration-resistant prostate cancer (mCRPC) as defined by Prostate Cancer Working Group 3 (PCWG3), preferably histologically confirmed adenocarcinoma of the prostate (adenocarcinoma with small cell or neuroendocrine (NE) features is permitted; however, small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed); (2) Measurable or evaluable mCRPC disease per Prostate Cancer Working Group 3 (PCWG3) criteria (the subject must have a serum PSA value greater than or equal to (>=2) nanograms per milliliter (ng / mL) at time of screening, or prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody); (3) Prior orchiectomy or medical castration; the subject who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and must continue this therapy throughout the treatment phase; and (4) Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In some embodiments, the subject does not meet any the following exclusion criteria: (1) History of solid organ or bone marrow transplantation; (2) Venous thromboembolic events (for example, pulmonary embolism) within 1 month prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody (uncomplicated (Grade <=2) deep vein thrombosis is not considered exclusionary); (3) Active autoimmune disease within the 12 months prior to signing consent or within the 12 months prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, that requires systemic immunosuppressive medications (for example, chronic corticosteroids, methotrexate, or tacrolimus); (4) Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study drug (antibiotic or antiviral prophylaxis is allowed); and (5) Any of the following within 6 months prior to signature of informed consent or within 6 months prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody: a. myocardial infarction, b. severe or unstable angina, c. clinically significant ventricular arrhythmias, d. congestive heart failure (New York Heart Association [NYHA] class II to IV), e. transient ischemic attack, and f. Cerebrovascular accident. In some embodiments, no Adverse Event of grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) is observed in the subject. In some embodiments, no event of Cytokine Release Syndrome (CRS) of Grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject. In some embodiments, no event of immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject. In some embodiments, no event of Injection Site Reaction (ISR) is observed in the subject. In some embodiments, no event of systemic Administration Related Reactions (sARRs) is observed in the subject. In some embodiments, no event of immune-related Adverse Event (irAE) is observed in the subject. In some embodiments, no event of hematologic toxicity of grade 3 or higher is observed in the subject. In some embodiments, no event of neutropenia of grade 3 or higher and no event of thrombocytopenia of Grade 3 or higher is observed in the subject, preferably no event of febrile neutropenia, no event of Grade 4 neutropenia for more than 7 days, no event of Grade 3 thrombocytopenia with clinically significant bleeding, and no event of Grade 4 thrombocytopenia with a duration of more than 7 days. In some embodiments, no event of non-hematological toxicity of Grade 3 or higher is observed in the subject. In some embodiments, no event of the following non-hematological toxicity is observed in the subject: - Grade 3 fatigue or asthenia; - Grade 3 fever; - Grade 3 nausea or grade 3 diarrhea; - Grade 3 hypertension; - Grade 3 alkaline phosphatase or GGT increase; - Grade 3 lipase or amylase increase; - Grade 3 electrolyte abnormality; - Grade 3 Adverse Event of tumor flare; and - First occurrence of a Grade 3 event of CRS, sARR or IRR. In some embodiments, no event of non-hematologic toxicity of grade 3 or higher and no event of hematologic toxicity of grade 3 or higher is observed in the subject. In some embodiments, no event of increase in aspartate aminotransferase (AST) or alkaline phosphatase (ALT) above 8 times the Upper Limit of Normal (ULN) is observed in the subject, or wherein no event of increase in AST or ALT above 5 times the ULN for more than 14 days is observed in the subject, or wherein no event of compliance with the Hy’Law criteria is observed in the subject (wherein the Hy’s law criteria are defined as ALT or AST value >3x ULN, and total bilirubin >2x ULN, and ALP <2x ULN, with no alternative etiology). In some embodiments, a Dose Limiting Toxicity (DLT) is not induced in the subject. In some embodiments, the probability that the DLT rate exceeds 30% in a cohort of at least 6 subjects, preferably in a cohort of 60-80 subjects, is lower than 95%. In some embodiments, the DLT comprises one or more event of the forgoing embodiments, preferably the hematological toxicity and non-hematological toxicity. In some embodiments, no confirmed disease progression (preferably, according to the Prostate Cancer Working Group 3 (PCWG3) Criteria (Scher et al.2016 Journal of Clinical Oncology 34(12): 1402-1418) is observed in the subject. In some embodiments, one or more of the PCWG3 disease Criteria are improved in the subject once he / she has received the isolated anti-hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody, compared to prior to the administration of the two bispecific antibodies; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody. In some embodiments, the serum Prostate-Specific Antigen (PSA) level of the subject decreases once he / she has received the isolated anti-hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody, compared to prior to the administration of the two bispecific antibodies; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody, preferably the serum PSA level decreases of 50% or more compared to prior to the administration of the two bispecific antibodies. In some embodiments, provide one or more events of improved efficacy chosen from among - increased T-cell activation; - increased T-cell infiltration into tumors; - improved T-cell mediated tumor killing; and - enhanced T-cell memory phenotypes; compared to prior to the administration of the isolated anti-hK2 / anti-CD3 bispecific antibody and of the isolated anti-PSMA / anti-CD28 bispecific antibody; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti- CD-28 bispecific antibody. In some embodiments, provide one or more events of improved efficacy chosen from among: - improved Objective Response Rate (ORR), where ORR is defined as the proportion of subjects who have a Partial Response or better according to RECIST v1.1 (Eisenhauer et al.2009 European Journal of Cancer 45: 228-247) without evidence of bone progression according to PCWG3; - improved PSA response rate (PSA50), where PSA50 is defined as the proportion of subjects with a percent change of 50% or more from baseline (e.g., compared to prior to treatment) in PSA; and - improved Duration Of Response (DOR), where DOR is defined as the time from the date of Partial Response or better to the date of first documented evidence of progressive disease, as defined in the PCWG3, or death due to any cause; compared to prior to the administration of the isolated anti-hK2 / anti-CD3 bispecific antibody and of the isolated anti-PSMA / anti-CD28 bispecific antibody; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti- CD-28 bispecific antibody. In some embodiments, the PSA50 is of more than 15%. SUBJECT MATTER DESCRIBED IN THE APPLICATION EMBODIMENTS 1. A method of treating prostate cancer in a human subject in need thereof, wherein an isolated anti-hK2 / anti-CD3 bispecific antibody and an isolated anti-PSMA / anti-CD28 bispecific antibody are both administered to the human subject, and wherein the method comprises: (1) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, and (2) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 3, 4.5, 15, 30, 45 or 90 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration, of the isolated anti-PSMA / anti-CD28 bispecific antibody. wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and wherein the first antigen binding domain comprises a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and wherein the third antigen binding domain comprises a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41; preferably the administering of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody provides a reduction in serum Prostate Specific Antigen (PSA), preferably an improved serum PSA reduction compared to administering the isolated anti-hK2 / anti-CD3 bispecific antibody at the same dose as the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody but without administering the anti-PSMA / anti-CD28 bispecific antibody, without triggering a cytokine release syndrome (CRS) of grade 3 or higher according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. The method of embodiment 1, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose), or is administered intravenously. The method of embodiment 2, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection, and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is 0.5-2000 mg per administration, preferably 50-800 mg per administration, such as 400 mg or 200 mg per administration. The method of embodiment 2, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific antibody is 0.5-1800 mg per administration, preferably 50-800 mg per administration, such as 75, 100, 150 or 300 mg per administration, particularly 75, 150 or 300 mg per administration. The method of any one of embodiments 1-4, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, such as by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose). The method of embodiment 5, wherein the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody is 0.5-2000 mg per administration, preferably 1.5-350 mg per administration, preferably 1.5-300 mg per administration, preferably 1.5-200 mg per administration, preferably 1.5-100 mg per administration, such as 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1.5, 4.5, 15, 45 or 90 mg per administration. The method of any one of embodiments 1-4, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. The method of embodiment 7, wherein the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody is 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 4.5, 15, 45 or 90 mg per administration. 9. The method of any one of embodiments 1-3, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration. 10. The method of embodiment 9, wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration. 11. The method of embodiment 9 or 10, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5 mg per administration. 12. The method of embodiment 9 or 10, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 4.5 mg per administration. 13. The method of embodiment 9 or 10, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 15 mg per administration. 14. The method of embodiment 9 or 10, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 45 mg per administration. 15. The method of embodiment 9 or 10, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 400 mg or 200 mg, preferably 400 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 90 mg per administration. 16. The method of any one of embodiments 9-15, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose). 17. The method of embodiment 16, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose). 18. The method of embodiment 16, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. 19. The method of any one of embodiments 1-3, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration. 20. The method of embodiment 19, wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration. 21. The method of embodiment 19 or 20, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5 mg per administration. 22. The method of embodiment 19 or 20, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 4.5 mg per administration. 23. The method of embodiment 19 or 20, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 15 mg per administration. 24. The method of embodiment 19 or 20, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 45 mg per administration. The method of embodiment 19 or 20, wherein the combination dose of the isolated anti- hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 90 mg per administration. The method of any one of embodiments 19 to 25, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. The method of embodiment 26, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose). The method of embodiment 26, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time). The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time). 31. The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time); wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time); and wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered is administered on the same day(s) as the combination dose of the isolated anti- hK2 / anti-CD3 bispecific antibody. 32. The method of any one of embodiments 1-28, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every three weeks, and wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered once every three weeks. 33. The method of any one of embodiments 1-28, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every two weeks, and wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered once every two weeks. 34. The method of any one of embodiments 1-28, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every six weeks, and wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered once every six weeks. 35. The method of any one of embodiments 1-28, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every week, and wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered once every week. 36. The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 37. The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every three weeks, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific is administered once every three weeks, and wherein the combination dose of the isolated anti- hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 38. The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every three weeks, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti- hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 400 mg or 200 mg per administration, preferably 400 mg per administration. 39. The method of any of the foregoing embodiments, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered once every three weeks, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific is administered once every three weeks, wherein the combination dose of the isolated anti- hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 400 mg or 200 mg per administration, preferably 400 mg per administration, and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration. 40. The method of any of the foregoing embodiments, further comprising administering to the subject an initial treatment dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of embodiment 1, preferably 5-10 days, such as 5, 6, 7, 8, 9, or 10 days, prior to the administering step (1) of embodiment 1. 41. The method of embodiment 37 or 40, wherein the initial treatment dose of the isolated anti- hK2 / anti-CD3 antibody is of the same dose level as the combination dose of this antibody or is lower than the combination dose of this antibody. 42. The method of embodiment 37, 38, 40 or 41, wherein the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, preferably 75, 150, 200 or 300 or 400 mg per administration, preferably 200 or 400 mg per administration, preferably 400 mg per administration. 43. The method of embodiment 39 or 42, wherein the initial treatment dose of the isolated anti- hK2 / anti-CD3 antibody is 400 mg per administration, the combination dose of this antibody is 400 mg per administration, and wherein the isolated anti-hK2 / anti-CD3 antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the initial treatment dose and / or of each combination dose respectively). 44. The method of embodiment 39 or 42, wherein the initial treatment dose of the isolated anti- hK2 / anti-CD3 antibody is 75, 100, 150 or 300 mg per administration, the combination dose of this antibody is 75, 100, 150 or 300 mg per administration respectively, and wherein the isolated anti-hK2 / anti-CD3 antibody is administered intravenously. 45. The method of any one of embodiments 37-44, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection, or wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered is administered intravenously. 46. The method of any of the foregoing embodiments, further comprising administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of embodiment 1, wherein the step-up doses are not higher than the combination dose of this antibody. 47. The method of embodiment 43 or 46, comprising administering to the subject a step-up dose of 30-70 mg per administration, such as 30, 40, 50, 60 or 70 mg per administration, preferably 50 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administering step (1) of embodiment 1, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administering step (1) of embodiment 1. 48. The method of any one of embodiments 37-47, further comprising administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administration of the initial treatment dose, wherein the step-up doses are not higher than the initial treatment dose. 49. The method of embodiment 45 or 48, comprising administering to the subject a step-up dose of 30-70 mg per administration, such as 30, 40, 50, 60 or 70 mg per administration, preferably 50 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose. The method of any one of embodiments 43-49, comprising administering to the subject a first step-up dose and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the second step-up dose, and wherein the second step-up dose is administered prior to the administering step (1) of embodiment 1 or the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administering step (1) of embodiment 1 or the administration of the initial treatment dose. The method of embodiment 47 or 50, wherein the first step-up dose is 5-25 mg per administration, such as 5, 10, 15, 20 or 25 mg per administration, preferably 10 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the second step-up dose is 30-70 mg per administration, such as 30, 40, 50, 60 or 70 mg per administration, preferably 50 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably, the second step-up dose is administered prior to the administration of the initial treatment dose. The method of any one of embodiments 43-51, wherein the one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody are administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each step-up dose). The method of any one of embodiments 43-48, comprising administering to the subject a step-up dose of 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose. The method of any one of embodiments 43-48, 50 and 53, comprising administering to the subject a first step-up dose and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the second step-up dose, and wherein the second step-up dose is administered prior to the administering step (1) of embodiment 1 or the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administering step (1) of embodiment 1 or the administration of the initial treatment dose. 55. The method of any one of embodiments 43-48, 50, 51, 53 and 54, wherein the first step-up dose is 2-5 mg per administration, such as 2, 2.5, 3, 3.5, 4, 4.5 or 5 mg per administration, preferably 3.5 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the second step-up dose is 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg per administration, preferably 18 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably, the second step-up dose is administered prior to the administration of the initial treatment dose. 56. The method of any one of embodiments 43-48 and 50-55, wherein the one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. 57. The method of any one of the foregoing embodiments, further comprising administering to the subject one or more step-up doses of the isolated anti-PSMA / anti-CD28 bispecific antibody prior to the initial administration of the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody, wherein the step-up doses are not higher than the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody. 58. A method of treating prostate cancer in a human subject in need thereof, comprising: (1) administering to the subject a combination dose of 400 mg per administration of an isolated anti-hK2 / anti-CD3 bispecific antibody once every 3 weeks, and (2) administering to the subject a combination dose of 1.5, 4.5, 15, 45 or 90 mg per administration of an isolated anti-PSMA / anti-CD28 bispecific antibody once every 3 weeks, wherein the administering of step (1) and the administering of step (2) are conducted on the same day, preferably the administering of step (2) is conduced within 1 hour after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody; wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2 and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; and the anti-PSMA / anti- CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41. 59. The method of embodiment 55 or 58, further comprising administering to the subject an initial treatment dose of 400 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering step (1) of embodiment 55, preferably the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is of the same dose level as the combination dose of this antibody or is lower than the combination dose of this antibody. 60. The method of embodiment 56 or 59, further comprising administering to the subject a step- up dose of 50 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific antibody 3- 8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, preferably the step-up dose of the isolated anti-hK2 / anti-CD3 antibody is of the same dose level as the initial treatment dose of this antibody or is lower than the initial treatment dose of this antibody. 61. The method of embodiment 56, 57, 59 or 60, further comprising administering to the subject a first step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and a second step- up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the second step-up dose, wherein the second step-up dose is administered prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, wherein the first step-up dose is 10 mg per administration, and wherein the second step-up dose is 50 mg per administration. 62. The method of any one of embodiments 55-61, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each step-up dose). 63. The method of any one of embodiments 55-62, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the or each step-up dose). 64. A method of treating prostate cancer in a human subject in need thereof, comprising: (1) administering to the subject a combination dose of 75 mg, 100 mg, 150 or 300 mg per administration of an isolated anti-hK2 / anti-CD3 bispecific antibody once every 3 weeks, and (2) administering to the subject a combination dose of 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration of an isolated anti-PSMA / anti-CD28 bispecific antibody once every 3 weeks, wherein the administering of step (1) and the administering of step (2) are conducted on the same day, preferably the administering of step (2) is conduced within 1 hour after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2 and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2 and a first HCDR3 of a first heavy chain variable region (VH1) of SEQ ID NO: 10, and a first light chain complementarity determining region (LCDR) 1, a first LCDR2, and a first LCDR3 of a first light chain variable region (VL1) of SEQ ID NO: 11; and the anti-PSMA / anti- CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41. 65. The method of embodiment 61 or 64, further comprising administering to the subject an initial treatment dose of 75 mg, 100 mg, 150 mg or 300 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific 1 week prior to the administering step (1) of embodiment 61, preferably the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is of the same dose level as the combination dose of this antibody or is lower than the combination dose of this antibody. 66. The method of embodiment 62 or 65, further comprising administering to the subject a step- up dose of 18 mg per administration of the isolated anti-hK2 / anti-CD3 bispecific antibody 3- 8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, preferably the step-up dose of the isolated anti-hK2 / anti-CD3 antibody is of the same dose level as the initial treatment dose of this antibody or is lower than the initial treatment dose of this antibody. 67. The method of embodiment 62, 63, 65 or 66 further comprising administering to the subject a first step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the second step-up dose, wherein the second step-up dose is administered prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose, wherein the first step-up dose is 3.5 mg per administration; and wherein the second step-up dose is 18 mg per administration. 68. The method of any one of the embodiments 61-67, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously. 69. The method of any one of the embodiments 61-68, wherein the isolated anti-PSMA / anti- CD28 bispecific antibody is administered intravenously. 70. The method of any one of the foregoing embodiments, wherein the second antigen binding domain of the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a second HCDR1, a second HCDR2, and a second HCDR3 of a second VH (VH2) of SEQ ID NO: 18 and a second LCDR1, a second LCDR2, and a second LCDR3 of a second VL (VL2) of SEQ ID NO: 19. 71. The method of any one of the foregoing embodiments, wherein the first antigen binding domain comprises a first HCDR1, a first HCDR2, a first HCDR3, a first LCDR1, a first LCDR2 and a first LCDR3 of SEQ ID NOs: 4, 5, 6, 7, 8, and 9, respectively. 72. The method of any one of the foregoing embodiments, wherein the first antigen binding domain comprises the VH1 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:10, and the VL1 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:11. 73. The method of any one of the foregoing embodiments, wherein the first antigen binding domain comprises the VH1 of SEQ ID NO:10, and the VL1 of SEQ ID NO:11. 74. The method of any one of the foregoing embodiments, wherein the first antigen binding domain comprises a Fab. 75. The method of any of the foregoing embodiments, wherein the second antigen binding domain comprises the second HCDR1, the second HCDR2, the second HCDR3, the second LCDR1, the second LCDR2 and the second LCDR3 of SEQ ID NOs: 12, 13, 14, 15, 16, and 17, respectively. 76. The method of any one of the foregoing embodiments, wherein the second antigen binding domain comprises the VH2 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:18, and the VL2 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:19. 77. The method of any one of the foregoing embodiments, wherein the second antigen binding domain comprises the VH2 of SEQ ID NO:18, and the VL2 of SEQ ID NO:19. 78. The method of any one of the foregoing embodiments, wherein the second antigen binding domain comprises an scFv. 79. The method of any one of the foregoing embodiments, wherein the second antigen binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:20. 80. The method of any one of the foregoing embodiments, wherein the first antigen binding domain comprises a Fab having a VH1 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 10, and a VL1 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 11; and the second antigen binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 20. 81. The method of any one of the foregoing embodiments, wherein the first antigen binding domain comprises a Fab comprising a VH1 having the amino acid sequence of SEQ ID NO:10 and a VL1 having the amino acid sequence of SEQ ID NO:11; and wherein the second antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO:20. 82. The method of any one of the foregoing embodiments, wherein the first antigen binding domain is linked to a first immunoglobulin (Ig) constant region or a fragment of the first Ig constant region and / or the second antigen binding domain is linked to a second immunoglobulin (Ig) constant region or a fragment of the second Ig constant region, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype. 83. The method of embodiment 79 or 82, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1 isotype. 84. The method of embodiment 79, 80, 81 or 82 wherein the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprises at least one mutation that results in reduced binding of the anti-hK2 / anti-CD3 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat. 85. The method of embodiment 81 or 84, wherein the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof. 86. The method of any one of embodiments 79-85, wherein the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprise one or more heterodimerization mutations to promote heterodimerization. 87. The method of embodiment 83 or 86, wherein the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V; or the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W. The method of any one of embodiments 79-87, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first heavy chain (HC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 21 and a first light chain (LC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 23, and a second heavy chain (HC2) that is at least 90%, 95% or 100% identical, to the amino acid sequence of SEQ ID NO: 24. The method of embodiment 85 or 88, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the HC1 having the amino acid sequence of SEQ ID NO: 21 or 22, the LC1 having the amino acid sequence of SEQ ID NO: 23 and the HC2 having the amino acid sequence of SEQ ID NO: 24. The method of any of the foregoing embodiments, wherein the fourth antigen binding domain of the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a fourth HCDR1, a fourth HCDR2, and a fourth HCDR3 of a fourth VH (VH4) of SEQ ID NO: 32, and a fourth LCDR1, a fourth LCDR2 and a fourth LCDR3 of a fourth VL (VL4) of SEQ ID NOs: 33, respectively. The method of any of the foregoing embodiments, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2, a third HCDR3, a third LCDR1, a third LCDR2, and a third LCDR3 of SEQ ID NO: 34, 35, 36, 37, 38, and 39, respectively. The method of any of the foregoing embodiments, wherein the fourth antigen binding domain comprises a fourth HCDR1, a fourth HCDR2, a fourth HCDR3, a fourth LCDR1, a fourth LCDR2, and a fourth LCDR3 of SEQ ID NO: 26, 27, 28, 29, 30, and 31, respectively. The method of any one of the foregoing embodiments, wherein the third antigen binding domain comprises a Fab, and the fourth antigen binding domain comprises an scFv, preferably the scFv comprises one or more cysteine substitutions. The method of any one of the foregoing embodiments, wherein the third antigen binding domain comprises a VH3 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 40, and a VL3 that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 41; and the fourth antigen binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 47. The method of any one of the foregoing embodiments, wherein the third antigen binding domain comprises a VH3 having the amino acid sequence of SEQ ID NO: 40 and a VL3 having the amino acid sequence of SEQ ID NO: 41; and the fourth antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO: 47. The method of any one of the foregoing embodiments, wherein the third antigen binding domain is linked to a third immunoglobulin (Ig) constant region or a fragment of the third Ig constant region, and / or the fourth antigen binding domain is linked to a fourth immunoglobulin (Ig) constant region or a fragment of the fourth Ig constant region, wherein the third Ig constant region or the fragment of the third Ig constant region and / or the fourth Ig constant region or the fragment of the fourth Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype. The method of embodiment 93 or 96, wherein one of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366S, L368A and Y407V, wherein the residues are numbered according to the EU index of Kabat. The method of embodiment 93, 94, 96 or 97, wherein the third and fourth Ig constant regions or the fragments thereof each comprise one or more mutations that result in reduced binding of the anti-PSMA / anti-CD28 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat. The method of embodiment 95 or 98, wherein the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof. . The method of any one of embodiments 93-99, wherein the third or fourth Ig constant regions or the fragment thereof further comprises purification mutations H435R and Y436F, wherein the residues are numbered according to the EU index of Kabat. . The method of any one of embodiments 93-100, wherein one of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / LT366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, wherein the residues are numbered according to the EU index of Kabat. 102. The method of any one of embodiments 93-101, wherein the isolated anti-PSMA / anti- CD28 bispecific antibody comprises a third heavy chain (HC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 44 and a third light chain (LC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 43, and a fourth heavy chain (HC4) that is at least 90%, at least 95% or 100% identical, to the amino acid sequence of SEQ ID NO: 42. 103. The method of embodiment 99 or 102, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the HC3 having the amino acid sequence of SEQ ID NO: 44, the LC3 having the amino acid sequence of SEQ ID NO: 43 and the HC4 having the amino acid sequence of SEQ ID NO: 42. 104. The method of any of the foregoing embodiments, wherein the prostate cancer is advanced prostate cancer. 105. The method of any of the foregoing embodiments, wherein the prostate cancer is metastatic prostate cancer. 106. The method of any of the foregoing embodiments, wherein the prostate cancer is metastatic castration-resistant prostate cancer (mCRPC). 107. The method of any of the foregoing embodiments, wherein the prostate cancer is mCRPC with histologically confirmed adenocarcinoma of the prostate. 108. The method of any of the foregoing embodiments, wherein the prostate cancer is mCRPC with a prostate adenocarcinoma that has small cell or neuroendocrine (NE) features. 109. The method of any of the foregoing embodiments, wherein the prostate cancer is mCRPC with a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma. 110. The method of any of the foregoing embodiments, wherein the subject has received: at least one androgen receptor (AR)-targeted therapy, such as a treatment with abiraterone acetate plus prednisone, apalutamide, enzalutamide, or darolutamide, or at least one chemotherapy, such as a treatment with docetaxel; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody , or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 111. The method of any one of the foregoing embodiments, wherein the subject has received - orchiectomy or medical castration; or has received - androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 112. The method of any of the foregoing embodiments, wherein the subject has not undergone orchiectomy, and the method further comprises administering to the subject a GnRH analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic, preferably before each administration of a combination dose of the isolated anti-hK2 / anti- CD3 bispecific antibody. 113. The method of any of the foregoing embodiments, further comprising administering to the subject at least one first additional therapeutic, prior to being administered with the combination dose of the anti-hK2 / anti-CD3 bispecific antibody, or at least prior to being administered with the initial combination dose of anti-hK2 / anti-CD3 bispecific antibody. 114. The method of embodiment 110 or 113, wherein the at least one first additional therapeutic is a glucocorticosteroid, antihistamine, antipyretic, or any combination thereof. 115. The method of embodiment 111 or 114, wherein the the glucocorticosteroid is dexamethasone, beclomethasone, betamethasone, budesonide, cortisone, hydrocortisone, methylprednisolone, prednisolone, prednisone, or triamcinolone, preferably dexamethasone. 116. The method of embodiment 111, 112, 114, or 115, wherein the antihistamine is diphenhydramine, brompheniramine, chlorpheniramine, clemastine, cypro.heptadine, dexchlorpheniramine dimenhydrinate, doxylamine, hydroxyzine, phenindamine, azelastine, loratadine, cetirizine, desloratadine, or fexofenadine, preferably diphenhydramine. 117. The method of any one of embodiments 111-116, wherein the antipyretic is acetaminophen, ibuprofen, naproxen, ketoprofen, and nimesulide, aspirin, choline salicylate, magnesium salicylate, sodium salicylate, or phenazone (antipyrine), preferably acetaminophen. 118. The method of any of the foregoing embodiments, further comprising administering to the subject at least one second additional therapeutic, prior to, and optionally after, being administered with the combination dose of anti-hK2 / anti-CD3 bispecific antibody, or at least prior to, and optionally after, being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 119. The method of embodiment 115 or 118, wherein the at least one second additional therapeutic is an H2-antagonist, a leukotriene inhibitor, an antiemetic, or any combination thereof. 120. The method of any of the foregoing embodiments, wherein the subject is a male subject. 121. The method of any one of the foregoing embodiments, wherein the subject is at least 18 years old. 122. The method of any of the foregoing embodiments, wherein the subject has received - at least one AR-targeted therapy, such as a treatment with abiraterone acetate plus prednisone, apalutamide, enzalutamide, or darolutamide, or - at least one chemotherapy, such as a treatment with docetaxel; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 123. The method of any of the foregoing embodiments, wherein the subject has received - orchiectomy or medical castration; or has received - androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 124. The method of any of the foregoing embodiments, wherein the subject meets one or more, preferably all of the following inclusion criteria: - Metastatic castration-resistant prostate cancer (mCRPC) as defined by Prostate Cancer Working Group 3 (PCWG3), preferably histologically confirmed adenocarcinoma of the prostate (adenocarcinoma with small cell or neuroendocrine (NE) features is permitted; however, small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed); - Measurable or evaluable mCRPC disease per Prostate Cancer Working Group 3 (PCWG3) criteria (the subject must have a serum PSA value greater than or equal to (>=2) nanograms per milliliter (ng / mL) at time of screening, or prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody); - Prior orchiectomy or medical castration; the subject who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and must continue this therapy throughout the treatment phase; and - Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 125. The method of any of the foregoing embodiments, wherein the subject does not meet any the following exclusion criteria: - History of solid organ or bone marrow transplantation; - Venous thromboembolic events (for example, pulmonary embolism) within 1 month prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody (uncomplicated (Grade <=2) deep vein thrombosis is not considered exclusionary); - Active autoimmune disease within the 12 months prior to signing consent or within the 12 months prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, that requires systemic immunosuppressive medications (for example, chronic corticosteroids, methotrexate, or tacrolimus); - Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study drug (antibiotic or antiviral prophylaxis is allowed); and - Any of the following within 6 months prior to signature of informed consent or within 6 months prior to the first dose of the isolated anti-hK2 / anti-CD3 bispecific antibody: a. myocardial infarction, b. severe or unstable angina, c. clinically significant ventricular arrhythmias, d. congestive heart failure (New York Heart Association [NYHA] class II to IV), e. transient ischemic attack, and f. Cerebrovascular accident. 126. The method of any of the foregoing embodiments, wherein no Adverse Event of grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) is observed in the subject. 127. The method of any of the foregoing embodiments, wherein no event of Cytokine Release Syndrome (CRS) of Grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject. 128. The method of any of the foregoing embodiments, wherein no event of immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject. 129. The method of any of the foregoing embodiments, wherein no event of Injection Site Reaction (ISR) is observed in the subject. 130. The method of any of the foregoing embodiments, wherein no event of systemic Administration Related Reactions (sARRs) is observed in the subject. 131. The method of any of the foregoing embodiments, wherein no event of immune-related Adverse Event (irAE) is observed in the subject. 132. The method of any of the foregoing embodiments, wherein no event of hematologic toxicity of grade 3 or higher is observed in the subject. 133. The method of any of the foregoing embodiments, wherein no event of neutropenia of grade 3 or higher and no event of thrombocytopenia of Grade 3 or higher is observed in the subject, preferably no event of febrile neutropenia, no event of Grade 4 neutropenia for more than 7 days, no event of Grade 3 thrombocytopenia with clinically significant bleeding, and no event of Grade 4 thrombocytopenia with a duration of more than 7 days. 134. The method of any of the foregoing embodiments, wherein no event of non- hematological toxicity of Grade 3 or higher is observed in the subject. 135. The method of any of the foregoing embodiments, wherein no event of the following non-hematological toxicity is observed in the subject: - Grade 3 fatigue or asthenia; - Grade 3 fever; - Grade 3 nausea or grade 3 diarrhea; - Grade 3 hypertension; - Grade 3 alkaline phosphatase or GGT increase; - Grade 3 lipase or amylase increase; - Grade 3 electrolyte abnormality; - Grade 3 Adverse Event of tumor flare; and - First occurrence of a Grade 3 event of CRS, sARR or IRR. 136. The method of any of the foregoing embodiments, wherein no event of non-hematologic toxicity of grade 3 or higher and no event of hematologic toxicity of grade 3 or higher is observed in the subject. 137. The method of any of the foregoing embodiments, wherein no event of increase in aspartate aminotransferase (AST) or alkaline phosphatase (ALT) above 8 times the Upper Limit of Normal (ULN) is observed in the subject, or wherein no event of increase in AST or ALT above 5 times the ULN for more than 14 days is observed in the subject, or wherein no event of compliance with the Hy’Law criteria is observed in the subject (wherein the Hy’s law criteria are defined as ALT or AST value >3x ULN, and total bilirubin >2x ULN, and ALP <2x ULN, with no alternative etiology). 138. The method of any of the foregoing embodiments, which does not induce a Dose Limiting Toxicity (DLT) in the subject. 139. The method of any of the foregoing embodiments, wherein the probability that the DLT rate exceeds 30% in a cohort of at least 6 subjects, preferably in a cohort of 60-80 subjects, is lower than 95%. 140. The method of embodiment 134, 135, 138 or 139 wherein the DLT comprises one or more of the events of embodiments 129-139, preferably the events of embodiment 130 or 133 (hematological toxicity) and the events of embodiment 132 or 135 (non-hematological toxicity). 141. The method of any of the foregoing embodiments, wherein no confirmed disease progression (preferably according to the Prostate Cancer Working Group 3 (PCWG3) Criteria (Scher et al.2016 Journal of Clinical Oncology 34(12): 1402-1418)) is observed in the subject. 142. The method of any of the foregoing embodiments, wherein one or more of the PCWG3 disease Criteria are improved in the subject once he / she has received the isolated anti- hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody, compared to prior to the administration of the two bispecific antibodies; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody. 143. The method of any of the foregoing embodiments, wherein the serum Prostate-Specific Antigen (PSA) level of the subject decreases once he / she has received the isolated anti- hK2 / anti-CD3 bispecific antibody and the isolated anti-PSMA / anti-CD28 bispecific antibody, compared to prior to the administration of the two bispecific antibodies; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody; preferably the serum PSA level decreases of 50% or more compared to prior to the administration of the two bispecific antibodies. 144. The method of any of the foregoing embodiments, which provides one or more events of improved efficacy chosen from among - increased T-cell activation; - increased T-cell infiltration into tumors; - improved T-cell mediated tumor killing; and - enhanced T-cell memory phenotypes; compared to prior to the administration of the isolated anti-hK2 / anti-CD3 bispecific antibody and of the isolated anti-PSMA / anti-CD28 bispecific antibody; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody. 145. The method of any of the foregoing embodiments, which provides one or more events of improved efficacy chosen from among: - improved Objective Response Rate (ORR), where ORR is defined as the proportion of subjects who have a Partial Response or better according to RECIST v1.1 (Eisenhauer et al. 2009 European Journal of Cancer 45: 228-247) without evidence of bone progression according to PCWG3; - improved PSA response rate (PSA50), where PSA50 is defined as the proportion of subjects with a percent decrease of 50% or more from baseline (e.g., compared to prior to treatment) in PSA; and - improved Duration Of Response (DOR), where DOR is defined as the time from the date of Partial Response or better to the date of first documented evidence of progressive disease, as defined in the PCWG3, or death due to any cause; compared to prior to the administration of the isolated anti-hK2 / anti-CD3 bispecific antibody and of the isolated anti-PSMA / anti-CD28 bispecific antibody; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody. 146. The method of any of the foregoing embodiments, wherein the PSA50 is of 15% or more than 15%. 147. An isolated anti-hK2 / anti-CD3 bispecific antibody for use in the method of any of the foregoing embodiments. 148. An isolated anti-PSMA / anti-CD28 bispecific antibody for use in the method of any of embodiments 1-146. 149. A method of treating prostate cancer in a human subject in need thereof, wherein an isolated anti-hK2 / anti-CD3 bispecific antibody and an isolated anti-PSMA / anti-CD28 bispecific antibody are both administered to the human subject, and wherein the method comprises: (1) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, and (2) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 3, 4.5, 15, 30, 45 or 90 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration, of the isolated anti-PSMA / anti-CD28 bispecific antibody. wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises the VH1 of SEQ ID NO:10, and the VL1 of SEQ ID NO:11; and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and wherein the third antigen binding domain comprises a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41; preferably the administering of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody provides a reduction in serum Prostate Specific Antigen (PSA), preferably an improved serum PSA reduction compared to administering the isolated anti-hK2 / anti-CD3 bispecific antibody at the same dose as the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody but without administering the anti-PSMA / anti-CD28 bispecific antibody, without triggering a cytokine release syndrome (CRS) of grade 3 or higher according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 150. The method of claim 149, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific antibody is 0.5-1800 mg per administration, preferably 50-800 mg per administration, such as 75, 100, 150 or 300 mg per administration, particularly 75, 150 or 300 mg per administration. 151. The method of claim 149, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, such as by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose). 152. The method of claim 151, wherein the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody is 0.5-2000 mg per administration, preferably 1.5-350 mg per administration, preferably 1.5-300 mg per administration, preferably 1.5-200 mg per administration, preferably 1.5-100 mg per administration, such as 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1.5, 4.5, 15, 45 or 90 mg per administration. 153. The method of claim 149, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously. 154. The method of claim 153, wherein the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody is 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 4.5, 15, 45 or 90 mg per administration. 155. The method of claim 149, wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration. 156. The method of claim 149, wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration. 157. The method of claim 149, wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time). 158. The method of claim 149, wherein the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time). 159. The method of claim 149, wherein the combination dose of the isolated anti-hK2 / the anti- CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 160. The method of claim 149, further comprising administering to the subject an initial treatment dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of claim 149, preferably 5-10 days, such as 5, 6, 7, 8, 9, or 10 days, prior to the administering step (1) of claim 149. 161. The method of claim 160, wherein the initial treatment dose of the isolated anti-hK2 / anti- CD3 antibody is of the same dose level as the combination dose of this antibody or is lower than the combination dose of this antibody. 162. The method of claim 160, wherein the initial treatment dose of the isolated anti-hK2 / anti- CD3 antibody is 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, preferably 75, 150, 200 or 300 or 400 mg per administration, preferably 200 or 400 mg per administration, preferably 400 mg per administration. 163. The method of claim 162, wherein the initial treatment dose of the isolated anti-hK2 / anti- CD3 antibody is 75, 100, 150 or 300 mg per administration, the combination dose of this antibody is 75, 100, 150 or 300 mg per administration respectively, and wherein the isolated anti-hK2 / anti-CD3 antibody is administered intravenously. 164. The method of claim 160, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection, or wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered is administered intravenously. 165. The method of claim 149, further comprising administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of claim 149, wherein the step-up doses are not higher than the combination dose of this antibody. 166. The method of claim 160, further comprising administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administration of the initial treatment dose, wherein the step-up doses are not higher than the initial treatment dose. 167. The method of claim 165, comprising administering to the subject a step-up dose of 15- 25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose. 168. The method of claim 165, comprising administering to the subject a first step-up dose and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the second step-up dose, and wherein the second step-up dose is administered prior to the administering step (1) of claim 149 or the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administering step (1) of claim 149 or the administration of the initial treatment dose. 169. The method of claim 165, wherein the first step-up dose is 2-5 mg per administration, such as 2, 2.5, 3, 3.5, 4, 4.5 or 5 mg per administration, preferably 3.5 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the second step-up dose is 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg per administration, preferably 18 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, preferably, the second step-up dose is administered prior to the administration of the initial treatment dose. 170. The method of claim 165, wherein the one or more step-up doses of the isolated anti- hK2 / anti-CD3 bispecific antibody is administered intravenously. 171. The method of claim 149, further comprising administering to the subject one or more step-up doses of the isolated anti-PSMA / anti-CD28 bispecific antibody prior to the initial administration of the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody, wherein the step-up doses are not higher than the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody. 172. The method of claim 149, wherein the first antigen binding domain comprises a Fab. 173. The method of claim 149, wherein the second antigen binding domain comprises the VH2 of SEQ ID NO:18, and the VL2 of SEQ ID NO:19. 174. The method of claim 149, wherein the second antigen binding domain comprises an scFv. 175. The method of claim 149, wherein the second antigen binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:20. 176. The method of claim 149, wherein the first antigen binding domain comprises a Fab comprising a VH1 having the amino acid sequence of SEQ ID NO:10 and a VL1 having the amino acid sequence of SEQ ID NO:11; and wherein the second antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO:20. 177. The method of claim 149, wherein the first antigen binding domain is linked to a first immunoglobulin (Ig) constant region or a fragment of the first Ig constant region and / or the second antigen binding domain is linked to a second immunoglobulin (Ig) constant region or a fragment of the second Ig constant region, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype. 178. The method of claim 177, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1 isotype. 179. The method of claim 177, wherein the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprises at least one mutation that results in reduced binding of the anti- hK2 / anti-CD3 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat. 180. The method of claim 179, wherein the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof. 181. The method of claim 177, wherein the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprise one or more heterodimerization mutations to promote heterodimerization. 182. The method of claim 181, wherein the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V; or the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W. 183. The method of claim 177, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first heavy chain (HC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 21 and a first light chain (LC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 23, and a second heavy chain (HC2) that is at least 90%, 95% or 100% identical, to the amino acid sequence of SEQ ID NO: 24. 184. The method of claim 183, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the HC1 having the amino acid sequence of SEQ ID NO: 21 or 22, the LC1 having the amino acid sequence of SEQ ID NO: 23 and the HC2 having the amino acid sequence of SEQ ID NO: 24. 185. The method of claim 149, wherein the third antigen binding domain comprises a Fab, and the fourth antigen binding domain comprises an scFv, preferably the scFv comprises one or more cysteine substitutions. 186. The method of claim 149, wherein the third antigen binding domain comprises a VH3 having the amino acid sequence of SEQ ID NO: 40 and a VL3 having the amino acid sequence of SEQ ID NO: 41; and the fourth antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO: 47. . The method of claim 149, wherein the third antigen binding domain is linked to a third immunoglobulin (Ig) constant region or a fragment of the third Ig constant region, and / or the fourth antigen binding domain is linked to a fourth immunoglobulin (Ig) constant region or a fragment of the fourth Ig constant region, wherein the third Ig constant region or the fragment of the third Ig constant region and / or the fourth Ig constant region or the fragment of the fourth Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype. . The method of claim 187, wherein one of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366S, L368A and Y407V, wherein the residues are numbered according to the EU index of Kabat. . The method of claim 187, wherein the third and fourth Ig constant regions or the fragments thereof each comprise one or more mutations that result in reduced binding of the anti-PSMA / anti-CD28 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat. . The method of claim 189, wherein the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof. . The method of claim 187, wherein the third or fourth Ig constant regions or the fragment thereof further comprises purification mutations H435R and Y436F, wherein the residues are numbered according to the EU index of Kabat. . The method of claim 187, wherein one of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / LT366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, wherein the residues are numbered according to the EU index of Kabat. . The method of claim 187, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third heavy chain (HC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 44 and a third light chain (LC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 43, and a fourth heavy chain (HC4) that is at least 90%, at least 95% or 100% identical, to the amino acid sequence of SEQ ID NO: 42. 194. The method of claim 193, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the HC3 having the amino acid sequence of SEQ ID NO: 44, the LC3 having the amino acid sequence of SEQ ID NO: 43 and the HC4 having the amino acid sequence of SEQ ID NO: 42. 195. The method of claim 149, wherein the prostate cancer is advanced prostate cancer. 196. The method of claim 149, wherein the prostate cancer is metastatic prostate cancer. 197. The method of claim 149, wherein the prostate cancer is metastatic castration-resistant prostate cancer (mCRPC). 198. The method of claim 149, wherein the prostate cancer is mCRPC with histologically confirmed adenocarcinoma of the prostate. 199. The method of claim 149 wherein the prostate cancer is mCRPC with a prostate adenocarcinoma that has small cell or neuroendocrine (NE) features. 200. The method of claim 149, wherein the prostate cancer is mCRPC with a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma. 201. The method of claim 149, wherein the subject has received: at least one androgen receptor (AR)-targeted therapy, such as a treatment with abiraterone acetate plus prednisone, apalutamide, enzalutamide, or darolutamide, or at least one chemotherapy, such as a treatment with docetaxel; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody , or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 202. The method of claim 149, wherein the subject has received - orchiectomy or medical castration; or has received - androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody. 203. The method of claim 149, wherein no Adverse Event of grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI- CTCAE) version 5.0) is observed in the subject. 204. The method of claim 149, wherein no event of Cytokine Release Syndrome (CRS) of Grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject. 205. The method of claim 149, wherein no event of immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject. 206. The method of claim 149, wherein no event of Injection Site Reaction (ISR) is observed in the subject. 207. The method of claim 149, wherein no event of systemic Administration Related Reactions (sARRs) is observed in the subject. 208. The method of claim 149, wherein no event of immune-related Adverse Event (irAE) is observed in the subject. 209. The method of claim 149, wherein no event of hematologic toxicity of grade 3 or higher is observed in the subject. 210. The method of claim 149, wherein no event of neutropenia of grade 3 or higher and no event of thrombocytopenia of Grade 3 or higher is observed in the subject, preferably no event of febrile neutropenia, no event of Grade 4 neutropenia for more than 7 days, no event of Grade 3 thrombocytopenia with clinically significant bleeding, and no event of Grade 4 thrombocytopenia with a duration of more than 7 days. 211. The method of claim 149, wherein no event of non-hematological toxicity of Grade 3 or higher is observed in the subject. 212. The method of claim 149, wherein no event of the following non-hematological toxicity is observed in the subject: - Grade 3 fatigue or asthenia; - Grade 3 fever; - Grade 3 nausea or grade 3 diarrhea; - Grade 3 hypertension; - Grade 3 alkaline phosphatase or GGT increase; - Grade 3 lipase or amylase increase; - Grade 3 electrolyte abnormality; - Grade 3 Adverse Event of tumor flare; and - First occurrence of a Grade 3 event of CRS, sARR or IRR. 213. The method of claim 149, wherein no event of non-hematologic toxicity of grade 3 or higher and no event of hematologic toxicity of grade 3 or higher is observed in the subject. 214. The method of claim 149, wherein no event of increase in aspartate aminotransferase (AST) or alkaline phosphatase (ALT) above 8 times the Upper Limit of Normal (ULN) is observed in the subject, or wherein no event of increase in AST or ALT above 5 times the ULN for more than 14 days is observed in the subject, or wherein no event of compliance with the Hy’Law criteria is observed in the subject (wherein the Hy’s law criteria are defined as ALT or AST value >3x ULN, and total bilirubin >2x ULN, and ALP <2x ULN, with no alternative etiology). 215. The method of claim 149, which does not induce a Dose Limiting Toxicity (DLT) in the subject. 216. The method of claim 149, wherein the probability that the DLT rate exceeds 30% in a cohort of at least 6 subjects, preferably in a cohort of 60-80 subjects, is lower than 95%. 217. The method of claim 216, wherein the DLT comprises one or more of the events of claims 209-216, preferably the events of claim 210 (hematological toxicity) and the events of claim 212 (non-hematological toxicity). 218. The method of claim 149, which provides one or more events of improved efficacy chosen from among - increased T-cell activation; - increased T-cell infiltration into tumors; - improved T-cell mediated tumor killing; and - enhanced T-cell memory phenotypes; compared to prior to the administration of the isolated anti-hK2 / anti-CD3 bispecific antibody and of the isolated anti-PSMA / anti-CD28 bispecific antibody; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody. 219. An isolated anti-hK2 / anti-CD3 bispecific antibody for use in the method of claim 149. 220. An isolated anti-PSMA / anti-CD28 bispecific antibody for use in the method of claim 149. EXAMPLES The following examples are provided to further describe some of the embodiments disclosed herein. The examples are intended to illustrate, not to limit, the disclosed embodiments. Example 1: A phase 1 study of an anti-PSMA / anti-CD28 bispecific antibody combined with an anti-hK2 / anti-CD3 bispecific antibody for treating advanced prostate cancer This is an open-label, multicenter, Phase 1 study to evaluate the safety, tolerability, and preliminary antitumor activity of an anti-PSMA / anti-CD28 bispecific antibody (“study PSMA x CD28 bispecific antibody”) when administered in combination with an anti-hK2 / anti-CD3 bispecific antibody (“study hK2 x CD3 bispecific antibody”). The sequences for each of the study bispecific antibodies are described herein and provided in the sequence listing. The participants are participants with prostate cancer, more particularly advanced prostate cancer including adult participants with mCRPC following at least 1 prior line of therapy. The purpose of the study is to determine recommended regimens for Phase 2 (RP2Rs) of combination of study PSMA x CD28 bispecific antibody with study hK2 x CD3 bispecific antibody (Part 1: dose escalation) and further evaluate the safety at RP2Rs (Part 2: dose expansion). Screening for eligible participants will be performed within 30 days before administration of the study intervention. Eligibility Criteria: Inclusion Criteria: each potential participant must satisfy all of the enrollment criteria for the study, which include: (1) must be 18 years or older; (2) have metastatic castration-resistant prostate cancer (mCRPC) as defined by Prostate Cancer Working Group 3 (PCWG3), and histologically confirmed adenocarcinoma of the prostate. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted, however, having small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed; (3) have measurable or evaluable disease per PCWG3 criteria, and must have a serum Prostate-Specific Antigen (PSA) value greater than or equal to 2 nanograms per milliliter ((>=2 ng / mL) at time of screening; (4) can have a prior or concurrent second malignancy (other than the disease under study) whose natural history or treatment is unlikely to interfere with any study endpoints of safety or efficacy; (5) have prior treatment with at least 1 prior AR-targeted therapy (i.e., abiraterone acetate plus prednisone, apalutamide, enzalutamide, darolutamide), or chemotherapy (e.g., docetaxel); (6) can have prior orchiectomy or medical castration, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), prior to the first dose of study drug and must continue this therapy throughout the treatment phase; (7) have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (8) have an estimated glomerular filtration rate (eGFR), based on the Modified Diet in Renal Disease (MDRD) 4-variable formula; (9) Participants are eligible if they have the hepatic function: Aspartate aminotransferase (AST) ≤3 x ULN Alanine aminotransferase (ALT) ≤3 x ULN Total bilirubin <1.5x ULN (isolated total bilirubin ≥1.5 x ULN with conjugated [direct] bilirubin <1.5xULN is allowed for those participants with known congenital nonhemolytic hyperbilirubinemias); (10) Participants should have hematology laboratory parameters within the following ranges, • independent of transfusion within 7 days, or growth factors within 3 weeks prior to first dose of study treatment: • hemoglobin ≥9.0 g / dL; • absolute neutrophil count ≥1.5 x 109 / L, (except for participants with benign ethnic neutropenia who may be enrolled with ANC ≥1.0 x 109 / L); and • Platelets ≥75×109 / L. Exclusion Criteria: Any potential participant who meets any of the following exclusion criteria for the study will be excluded from participating in the study: (1) any of the following medical conditions: - history of solid organ or bone marrow transplantation; - venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study drug; uncomplicated (Grade <=2) deep vein thrombosis is not considered exclusionary - active autoimmune disease within the 12 months prior to signing consent that requires systemic immunosuppressive medications (example, chronic corticosteroids, methotrexate, or tacrolimus) - active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study drug. Antibiotic or antiviral prophylaxis is allowed; - any of the following within 6 months prior to signature of informed consent: a. myocardial infarction, b. severe or unstable angina, c. clinically significant ventricular arrhythmias, d. congestive heart failure (New York Heart Association [NYHA] class II to IV), e. transient ischemic attack, and f. Cerebrovascular accident; - Clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use (>2 L / min by nasal cannula) to maintain adequate oxygenation (2) known malignant central nervous system (CNS) or leptomeningeal disease; (3) active hepatitis of infectious origin; and (4) certain restrictions on prior / concomitant therapy or clinical Study Experience. Interventions Each of the anti-PSMA / anti-CD28 bispecific antibody and the anti-hK2 / anti-CD3 bispecific antibody under the study is administered subcutaneously (SC) or intravenously (IV). GnRH analog therapy (leuprolide, goserelin, degarelix, relugolix, or triptorelin) is administered in participants who have undergone orchiectomy for the duration of treatment while in this study. Participants will receive an anti-PSMA / anti-CD28 bispecific antibody combined with an anti-hK2 / anti-CD3 bispecific antibody during Part 1 (dose escalation). The dose of the anti- PSMA / anti-CD28 bispecific antibody will be escalated sequentially until one or more recommended phase 2 regimens (RP2Rs) are achieved. Participants will receive the combination treatment at the RP2Rs in Part 2 (dose expansion). Participants who have not undergone orchiectomy must continue gonadotropin-releasing hormone (GnRH) analog therapy for the duration of treatment while in this study. Different timing of the first combination dose following the initial full treatment dose of study hK2 x CD3 bispecific antibody may be explored; step-up doses of study PSMA x CD28 bispecific antibody may also be introduced to mitigate risks of cytokine release syndrome (CRS), one of the principal toxicities of concern for any CD3 redirector. The first combination dose of study PSMA x CD28 bispecific antibody will be administered approximately 1 week after the initial treatment dose of study hK2 x CD3 bispecific antibody. The exposure to study hK2 x CD3 bispecific antibody prior to initiating combination dosing is incorporated to minimize risks for cytokine mediated toxicity. An initial treatment dose level for study hK2 x CD3 bispecific antibody is 400 mg, SC, every 3 weeks (Q3W), with at least 2 step-up doses (10 mg and 50 mg, SC) to mitigate CRS. At each combination dose, study PSMA x CD28 bispecific antibody will be given within 1 hour after the end of administration of study hK2 x CD3 bispecific antibody on the same day. A starting dose for study PSMA x CD28 bispecific antibody is 1.5 mg, SC. Combination dose levels will proceed with no more than half-log incremental increases in study PSMA x CD28 bispecific antibody given with study hK2 x CD3 bispecific antibody with at least 3 participants per cohort. Escalation decisions will be guided by BOIN. If the planned starting dose for study PSMA x CD28 bispecific antibody is not tolerable when combined with study hK2 x CD3 bispecific antibody 400 mg, SC, then study hK2 x CD3 bispecific antibody could be reduced. See Table 1 for the provisional SC dosing for Part 1 of the study. Table 1 Dose Level Anti-PSMA / CD28 Bispecific (mg) Anti- hK2 / CD3 Bispecific (mg) FIG.1 illustrates an example of the initial drug administration schedule that will be evaluated in Part 1 based on Q3W dosing of both agents. In particular, the step-up doses and treatment dose 1 of study hK2 x CD3 bispecific antibody will be given before combination dosing with study PSMA x CD28 bispecific antibody is initiated. Dose Limiting Toxicity (DLT) will be assessed. The DLT period is 21 days and begins after the first combination dose. The DLT period excludes step-up and initial study hK2 x CD3 bispecific antibody single-agent treatment doses. The DLT period will be adjusted if other dosing schedules are explored as appropriate. Participants who do not complete the DLT period or have not completed the planned single agent or combination doses regimen during the DLT period for reasons other than for toxicities may be replaced at the discretion of the SET. Dosing in the current study will be initiated with 2 step-up doses of study hK2 x CD3 bispecific antibody at 10 mg and 50 mg SC weekly followed by the starting treatment dose of study hK2 x CD3 bispecific antibody at 400 mg SC Q3W. The step-up doses and first treatment dose will be administered 3 to 7 days apart. The FIH starting dose for study PSMA x CD28 bispecific antibody in combination with study hK2 x CD3 bispecific antibody was determined to be 1.5 mg via SC administration. The initial treatment dose of study hK2 x CD3 bispecific antibody at 400 mg SC in the current study provides a safety margin and mitigates the potential for altered frequency and severity of CRS risks by combining with study PSMA x CD28 bispecific antibody. Although the study will be initiated with Q3W treatment doses, alternative dosing schedules (e.g., Q1W, Q2W, Q6W, etc.) may be evaluated based on emerging safety and pharmacokinetic data after approval by the SET. The study hK2 x CD3 bispecific antibody can also be administered intravenously, e.g., at a combination dose of 0.5-1800 mg per administration, preferably 50-800 mg per administration, such as 75, 100, 150 or 300 mg per administration, particularly 75, 150 or 300 mg per administration. The study PSMA x CD28 bispecific antibody can also be administered intravenously, e.g., with an escalating dose of 0.5 to 100 mg, particularly 0.5 to 81 mg, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration. Outcome Measures Primary Outcome Measures In Part 1, the number of participants with DLT, up to 21 days after first dose of study drug, will be measured. DLTs are specific adverse events (AEs) and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity. In Part 1 and Part 2, the number of participants with Adverse Events (AEs) by severity will be measured up to 3 years 7 months after the first dose of study drug. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical / biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of CRS and immune effector cell-associated neurotoxicity syndrome events, which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. Secondary Outcome Measures In addition to the primary outcome measures, secondary outcome measures, such as those shown in Table 2 below, will also be measured.

[0002] Table 2 Outcome Measure Time Frame Description Part 2: Serum Pre-dose up to 336 Serum samples will be analyzed to determine ic m 8 l. 2 Objective Response Rate Up to 3 years 7 ORR is defined as the proportion of participants (ORR) months who have a partial response (PR) or better d of f of r abdomen, and pelvis (MRI may be used if needed), measurement of serum PSA and whole-body bone scans using technetium-99. Blood samples will be collected to characterize the PK and assess anti-drug antibodies (ADA) for study PSMA x CD28 bispecific antibody and study hK2 x CD3 bispecific antibody. Blood samples will also be collected to evaluate progressive disease (PD) biomarkers that may be predictive of response or resistance to bispecific antibody therapy. Participants may be enrolled in pharmacokinetic / pharmacodynamic (PK / PD) cohorts with required on-treatment and optional pretreatment tumor biopsies to assess changes in biomarkers in the TME following combination treatment in Part 1 and Part 2. Selected PK / PD cohorts may also undergo additional blood sample collections. The safety of study PSMA x CD28 bispecific antibody in combination with study hK2 x CD3 bispecific antibody will be evaluated by physical examinations, vital signs, ECOG performance status, electrocardiograms, clinical laboratory tests, and AE monitoring including assessment of DLTs. The severity of AEs will be assessed per NCI-CTCAE version 5.0. CRS and associated neurologic events (i.e., ICANS events) will be graded for severity according to ASTCT guidelines. A further Phase 1 study was conducted to evaluate the recommended phase 2 dose(s) (RP2Ds) of the hK2 x CD3 bispecific antibody in Part 1 (Dose Escalation) and the safety at the RP2Ds in Part 2 (Dose Expansion) in patients with (advanced) prostate cancer (mCRPC patients). The study provides the number of participants with Adverse Events when receiving the hK2 x CD3 bispecific antibody by IV administration or by SC administration. Example 2. Effects of Study PSMA x CD28 Bispecific Antibody in Mouse T-cell Redirection Xenograft Tumor Models The antitumor activity and pharmacodynamics (PD) relationship of study PSMA x CD28 bispecific antibody alone or in combination with study hK2 x CD3 bispecific antibody (KLK2xCD3) (same antibodies as example 1) were evaluated in established SC human prostate VCaP PSMA+ / KLK2+xenografts in T-cell humanized male NSG mice in which study PSMA x CD28 bispecific antibody treatment or in combination with study hK2 x CD3 bispecific antibody was initiated after palpable tumors were formed (NSG = non-obese diabetic (NOD) severe combined immunodeficiency (scid) gamma). Combination treatment of study PSMA x CD28 bispecific antibody with study hK2 x CD3 bispecific antibody induced significant antitumor activity, and activity was associated with an enhancement of T-cells recruitment to tumors and study PSMA x CD28 bispecific antibody binding to human T cells. In the study, male NSG mice were randomized into groups of 10 animals each 20 days post SC VCaP cell implantation, such that all groups had mean tumor volume values of 122 mm3. Mice were injected with human T cells on Day 21, and antibody treatment was initiated 1 day post T-cell implantation, on Day 22. Mice were IP dosed twice weekly for a total of 8 doses with: study PSMA x CD28 bispecific antibody at 3 mg / kg; study hK2 x CD3 bispecific antibody at 1 mg / kg; the combination of study PSMA x CD28 bispecific antibody at 0.1, 0.3, 1, or 3 mg / kg administered concurrently with study hK2 x CD3 bispecific antibody at 1 mg / kg; or DPBS. Significant antitumor efficacy of VCaP xenografts was observed with study hK2 x CD3 bispecific antibody (single agent) treatment at 1 mg / kg as assessed by change in growth rate over time (p≤0.05), with 43% change in tumor growth inhibition (ΔTGI) as compared to DPBS- treated control mice on Day 44 post tumor implantation (FIG.2). Study PSMA x CD28 bispecific antibody (single agent) treatment at 3 mg / kg did not result in significant antitumor activity and TGI was not observed as compared with DPBS control. Significant antitumor efficacy was observed with combination treatment of study hK2 x CD3 bispecific antibody at 1 mg / kg and study PSMA x CD28 bispecific antibody at either 0.1, 0.3, 1, or 3 mg / kg as assessed by change in growth rate over time (p≤0.05), with 90%, 88%, 90%, and 89% ΔTGI, respectively, as compared to DPBS control treatment on Day 44 post tumor implantation. Additionally, the combination treatment of study PSMA x CD28 bispecific antibody at 0.3, 1, and 3 mg / kg + study hK2 x CD3 bispecific antibody at 1 mg / kg resulted in 1 of 10, 2 of 10, and 1 of 10 mice showing complete tumor regressions (CRs), respectively, at end of study on Day 55. Partial tumor regressions (PRs, defined as a tumor volume on the final day of analysis smaller than that of the initial tumor volume) were also observed in 4 of 10, 4 of 10, and 3 of 10 mice in the combination treatment of study PSMA x CD28 bispecific antibody at 0.1, 0.3, and 1 mg / kg + study hK2 x CD3 bispecific antibody at 1 mg / kg, respectively. Significant antitumor efficacy was observed in all combination-therapy-treated groups compared with either single Ab treatment as assessed by change in growth rate (p≤0.05). Dose dependency of study PSMA x CD28 bispecific antibody was not observed at the doses and dosing frequency selected. In an efficacy study, tumors from mice bearing established SC VCaP xenografts were collected to evaluate PD effects by IHC analysis of T-cell infiltration. Tumors were collected from 3 animals per treatment group from mice treated with study hK2 x CD3 bispecific antibody at 1 mg / kg or study PSMA x CD28 bispecific antibody 1 mg / kg + study hK2 x CD3 bispecific antibody 1 mg / kg or DPBS at 24 hours post fourth dose. Tumors were stained for the presence of intra-tumoral CD3+ T-cell infiltration. Representative micrographs of immunostained tumors demonstrated an increase in CD3+ T-cell infiltration in VCaP tumors in the combination-therapy study PSMA x CD28 bispecific antibody 1 mg / kg + study hK2 x CD3 bispecific antibody 1 mg / kg group as compared to the DPBS control-treated and study hK2 x CD3 bispecific antibody 1 mg / kg single agent groups (FIG.3). These results demonstrate that combination treatment with study PSMA x CD28 bispecific antibody + study hK2 x CD3 bispecific antibody results in enhanced recruitment of T cells to the tumor, concurrent with elimination of tumor cells. Example 3. Study PSMA x CD28 Bispecific Antibody Mediated Enhancement of Cytotoxicity, T-cell Activation, and Cytokines Production when Combined with Fixed Dose of Study hK2 x CD3 Bispecific Antibody The ability of study PSMA x CD28 bispecific antibody to enhance cytotoxicity, T-cell activation and cytokine release was evaluated using PBMC from 5 healthy donors co-cultured with double positive antigen PSMA+ / KLK2+ VCaP cells or double negative antigen PSMA- / KLK2- DU145 cells. To test the ability of study PSMA x CD28 bispecific antibody to enhance T-cell- dependent cytotoxicity function and T-cell activation and assess the degree of cytokine release when dosed alone and when combined with study hK2 x CD3 bispecific antibody, a full dose range of single-agent study hK2 x CD3 bispecific antibody was evaluated in a cytotoxicity assay (same antibodies as example 1). This identified an EC20 value of study hK2 x CD3 bispecific antibody to be used as a fixed dose in combination with study PSMA x CD28 bispecific antibody. Cells treated with a fixed EC20 dose of study hK2 x CD3 bispecific antibody combined with the full dose range of study PSMA x CD28 bispecific antibody demonstrated, in a concentration-dependent manner, enhanced T-cell-mediated target cell cytotoxicity, T-cell activation and cytokine release levels compared to study hK2 x CD3 bispecific antibody EC20 treatment alone (FIG.4). Combination treatment of a Null×CD28 control antibody with a fixed EC20 dose of study hK2 x CD3 bispecific antibody demonstrated no enhanced activity of T cells. Additionally, no T-cell activity was observed from conditions treated with study PSMA x CD28 bispecific antibody or Null×CD28 alone. Finally, to confirm that enhanced T-cell activity from combination treatment with study PSMA x CD28 bispecific antibody was antigen dependent, identical assays were performed using double negative antigen PSMA– / KLK2– DU145 cells. No cytotoxicity, T cell activation, or cytokine release was observed in DU145 cells, indicating that the in vitro enhanced activity was PSMA-dependent. Example 4. Repeat-Dose Toxicity Safety pharmacology endpoints were included in a 4-week GLP-compliant toxicology study in cynomolgus monkeys (same antibody as example 1). There were no study PSMA x CD28 bispecific antibody-related effects when assessed after 2- and 4-weeks of dose administration in cardiovascular parameters (heart rate, QT, QRS, PR via ECGs), body temperature (2-3, 5-6, and 10-12 hours post dose on Day 1, 8, 15, and 22), respiration rates (assessed during weeks 2 and 4), neurological function at subcutaneous doses of 1 and 10 mg / kg administered once a week for 4 doses. An assessment dedicated to neurological changes was conducted during week 4. Weekly detailed examinations and veterinary examinations during week 2 and 4 also checked for any neurologic abnormalities. Exposure at the high dose of 10 mg / kg was Cmax (Day 22): 277 μg / mL and AUC0-7d (Day 22): 1840 μg day / mL. A 4-week GLP-compliant toxicology study was conducted in sexually mature cynomolgus monkeys (3 males / group) with a once weekly subcutaneous dose administration of study PSMA x CD28 bispecific antibody (TOX15296, Table 3) at doses of 0, 1, and 10 mg / kg. Sexually mature cynomolgus monkeys were used for this study as they were considered more relevant to the target human population being treated for prostate cancer. Table 3: Mean PK parameters for study PSMA x CD28 bispecific antibody following IV administration in cynomolgus monkeys Test Route Dose Number of Exposure Findings Material Level NHPs e e e g y, y g y y, observations, body weights (weekly), ophthalmic exams, cardiovascular parameters (heart rate, QT, QRS, PR via ECGs), body temperature, respiration rates, neurological function, hematology, clinical chemistry, coagulation, urinalysis, cytokines, immunophenotyping, organ weights, gross pathology, microscopic pathology, toxicokinetics, and ADA. Animals were administered study PSMA x CD28 bispecific antibody doses 1 or 10 mg / kg 1x weekly for 4 weeks after which all animals were euthanized, and tissues collected at necropsy. All doses were tolerated with no study PSMA x CD28 bispecific antibody-related adverse effects in any of the parameters tested. The study PSMA x CD28 bispecific antibody-related hematology parameters were limited to a pattern of minimally to moderately decreased lymphocytes observed 1, 24, and 48 hours following each dose at ≥ 1 mg / kg for the first 3 weeks with a return to baseline between doses. After the fourth dose, lymphocyte decreases persisted until the last time point assessed (168 hours post the last dose). These decreases lacked noteworthy correlative changes in immunophenotyping 48 hours postdose (immunophenotyping analyses were not performed at the other postdose time points). The administration of the PSMA x CD28 bispecific antibody was considered a contributing factor to the lymphocyte decreases but not the sole cause, given a similar pattern of lesser magnitude in the control animals. Importantly, there was no indication of CD28 mediated T-cell activation including super agonism. There were no study PSMA x CD28 bispecific antibody-related changes in any of the measured cytokine plasma concentrations, at any time point evaluated (Day 1 and Day 22: Pre, 2, 6, and 24 hour postdose) in comparison to the respective pre-study and / or control values. These cytokines included: IL-1β, IL-1ra, IL-2, IL-5, IL 6, IL-12 / 23 (p40), IL-13, IL-17A, IFN-γ, TNF-α, G-CSF, or GM-CSF. Moreover, there were no apparent PSMA x CD28 bispecific antibody related changes in T-lymphocytes, including T- helper and T-cytotoxic lymphocyte subsets, B-lymphocytes, natural killer cells, or expression of CD25, CD69 or Ki67 as evaluated by immunophenotyping compared to the control group (Day 1, Day 8 and Day 15: Pre, 48 hour postdose and on Day 22 Pre, 48 hour postdose and 168 hour postdose. No ADA was observed in the 10 mg / kg dose group but ADA was observed in 2 / 3 animals in the 1 mg / kg dose group. Exposures between dose groups were approximately dose proportional. The NOAEL was 10 mg / kg, the highest dose tested. Example 5. Single-dose Pharmacokinetics in cynomolgus monkeys The PK profile of the study PSMA x CD28 bispecific antibody (same antibody as example 1) was evaluated in male cynomolgus monkeys (n=6) following a single dose of 0.0007, 0.0375, 0.5 or 3 mg / kg, IV administration (CP2022-PK-056). Only one time-point above LLOQ was captured at 0.0007 mg / kg dose and hence this dose could not be incorporated in the PK analysis. The study PSMA x CD28 bispecific antibody exposure (AUCinf) increased in a greater than dose-proportional manner following a single IV dose in the dose range of 0.0375 to 3 mg / kg. An 80-fold increase in dose from 0.0375 to 3 mg / kg resulted in a 767-fold increase in AUCinf. This is consistent with a TMDD profile. Table 4: Study Design and Findings Mean PK Parameters Dose (mg / kg) 0.0375 0.5 3 . The study PSMA x CD28 bispecific antibody was evaluated in a cytokine release hazard identification assay with a dry coat method to assess the potential of study PSMA x CD28 bispecific antibody to mediate cytokine release that could suggest potential for superagonism (same antibody as example 1). Human PBMCs from 10 healthy donors were incubated with study PSMA x CD28 bispecific antibody, clinical comparator monoclonal antibody (mAb; Opdivo®), positive control (anti-CD28 superagonistic ANC28.1 / 5D10 human anti-CD28 mAb) or isotype controls (Null×CD28 and Null×PSMA). The study PSMA x CD28 bispecific antibody or comparators were dry coated onto wells of a 96-well microtiter plate at 0.04 to 10 μg / well. After incubation, the supernatants were harvested and analyzed for interleukin (IL)-1 ^, IL-2, IL- 4, IL-6, IL-8, IL-10, IL-12P70, interferon (IFN)- ^, and tumor necrosis factor (TNF)- ^. There was no evidence supporting risk of a superagonist potentiated cytokine release in any donors with the study PSMA x CD28 bispecific antibody or Null×CD28 bispecific antibodies. The superagonistic CD28 mAb (positive control) elicited a cytokine profile associated with cytokine release syndrome; increases were observed in IL-1 ^ (6 / 10 donors), IL2 (10 / 10 donors), IL4 (10 / 10 donors), IL6 (9 / 10 donors), IL8 (10 / 10 donors), IL10 (10 / 10 donors), IFN- ^ ( ^ ^ ^ ^ ^ donors), and TNF- ^ ( ^ ^ ^ ^ ^ donors). In 2 of 10 donors, increases in IL-I ^ and IL-6 were observed with the all 3 bi-specific antibodies tested: PSMA×CD28, Null×CD28 and Null×PSMA. IL-I ^ and IL-6 were increased up to 26x and 41x relative to PBS and / or clinical comparator, Opdivo®, a marketed checkpoint inhibitor with low risk of cytokine release syndrome. The data supports that the potential for IL- I ^ and IL-6 increase is not due to either PSMA or CD28 targeting, but a potential interaction with other areas of the bispecific molecule with myeloid cells in the PBMC milieu of these 2 donors. Given the qualitative nature of this substrate bound (dry coat), hazard ID platform, a translatable concentration at which the increases occur is not appropriately determinable. Overall, this hazard identification evaluation does support the consideration of the potential for study PSMA x CD28 bispecific antibody to mediate IL-1 ^ and IL-6 increases in human PBMCs but does not support a risk of CD28 superagonism-mediated cytokine release. Example 7. Combination treatment studies to determine MABEL As shown in FIG.4, study PSMA x CD28 bispecific antibody treatment alone did not yield any T-cell activity, thus MABEL for study PSMA x CD28 bispecific antibody can only be determined from combination treatments, and at a physiologically relevant E:T ratio. MABEL for co-stimulation is defined as the EC50 at which study PSMA x CD28 bispecific antibody can potentiate the in vitro activity of study hK2 x CD3 bispecific antibody, when combined with study hK2 x CD3 bispecific antibody at a fixed concentration (same antibodies as example 1). To determine the Minimal Anticipated Biological Effect Level (MABEL), in vitro studies (Example 3) were performed and established that study PSMA x CD28 bispecific antibody treatment alone did not yield any T-cell activity. The MABEL for study PSMA x CD28 bispecific antibody was only discernable using combination treatments with study hK2 x CD3 bispecific antibody, and at a physiologically relevant effector to target cells (E:T) ratio. MABEL for co-stimulation is defined as the EC50 at which study PSMA x CD28 bispecific antibody can potentiate the in vitro activity of study hK2 x CD3 bispecific antibody, when combined with study hK2 x CD3 bispecific antibody at a fixed concentration. Before evaluating combination treatments for MABEL, single-agent treatment of study hK2 x CD3 bispecific antibody was evaluated in a T-cell activation assay, measuring CD69 upregulation at 48 hours (early activation marker) to identify values of EC90, EC50, EC20, and one-third of EC20. These ECX values were used as fixed doses in combination treatments with full dose range of study PSMA x CD28 bispecific antibody. VCaP cells that coexpress PSMA and KLK2 were co-cultured with PBMCs from 5 healthy donors in the presence of full-dose range of study PSMA x CD28 bispecific antibody combined with various fixed doses of study hK2 x CD3 bispecific antibody (one third of EC20 to EC90). VCaP is a well characterized primary human cell line derived from a metastatic bone lesion of human prostate cancer and has been shown to be sensitive to PSMA and KLK2 therapies. An E:T ratio of 1:5 was used as a conservative estimate to set the starting dose based on reports of low T-cell infiltrates occurring in the mCRPC tumor microenvironment. Combination treatments were assessed in three different assays: T-cell activation, cytokine release, and cytotoxicity. The most sensitive readout used to determine MABEL concentration was T-cell activation as assessed by flow cytometry measuring CD69 upregulation at 48 hours. Study PSMA x CD28 bispecific antibody demonstrated enhanced T-cell activation in a concentration-dependent manner when combined with each of the study hK2 x CD3 bispecific antibody fixed doses compared to conditions with study hK2 x CD3 bispecific antibody fixed doses alone. T-cell activation was assessed by flow cytometry, measuring CD69 upregulation at 48 hours (FIG.5). Study PSMA x CD28 bispecific antibody EC50 value was identified from combination treatment with fixed EC90 of study hK2 x CD3 bispecific antibody and it was selected to determine MABEL concentration. The lowest median EC50 value of T-cell activation for study PSMA x CD28 bispecific antibody, identified from combination treatment with fixed EC90 of study hK2 x CD3 bispecific antibody, was chosen to determine the MABEL concentration of 6 ng / mL (0.048 nM). This value represents the estimated Cmax following SC administration based on the totality of the data and incorporating data from other CD3-redirector programs that are in clinical development. Based on this, the FIH starting dose for study PSMA x CD28 bispecific antibody in combination with study hK2 x CD3 bispecific antibody was determined to be 1.5 mg via SC administration, derived from an approximate 18.75 μg / kg dose with assumed median body weight of 80 kg for patients with prostate cancer. The use of results from in vitro T-cell activation experiments were consistent with the recommendations by the European Medicines Agency and US FDA Guidance (EMA 2018, Saber 2017).

[0003] SEQUENCE LISTING SEQ ID NO Sequence Description 1 MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGT Human CD3 epsilon DIQMTQSPSSLSASVGDRVTITCRARQSIGTAIHWYQQKPGKAP VL of anti-CD3 in study hK2xCD3 KLLIKYASESISGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ bispecific antibody SGSWPYTFGQGTKLEIK 3 3 3 al 3 3 al LPAPIEKTISKAKGQPREPQVYVYPPSREEMTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFALVSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK x x CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL WCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK is

Claims

CLAIMS We claim:

1. A method of treating prostate cancer in a human subject in need thereof, wherein an isolated anti-hK2 / anti-CD3 bispecific antibody and an isolated anti-PSMA / anti-CD28 bispecific antibody are both administered to the human subject, and wherein the method comprises: (1) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, and (2) administering to the subject a combination dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 3, 4.5, 15, 30, 45 or 90 mg per administration, more particularly 1.5, 4.5, 15, 30, 45 or 90 mg per administration, of the isolated anti-PSMA / anti-CD28 bispecific antibody. wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first antigen binding domain that binds specifically to hK2, and a second antigen binding domain that binds specifically to CD3ε, wherein the first antigen binding domain comprises the VH1 of SEQ ID NO:10, and the VL1 of SEQ ID NO:11; and wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third antigen binding domain that binds specifically to PSMA, and a fourth antigen binding domain that binds specifically to CD28, wherein the third antigen binding domain comprises a third HCDR1, a third HCDR2 and a third HCDR3 of a third heavy chain variable region (VH3) of SEQ ID NO: 40, and wherein the third antigen binding domain comprises a third light chain complementarity determining region (LCDR) 1, a third LCDR2, and a third LCDR3 of a third light chain variable region (VL3) of SEQ ID NO: 41; preferably the administering of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody and the combination dose of the isolated anti-PSMA / anti-CD28 bispecificantibody provides a reduction in serum Prostate Specific Antigen (PSA), preferably an improved serum PSA reduction compared to administering the isolated anti-hK2 / anti-CD3 bispecific antibody at the same dose as the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody but without administering the anti-PSMA / anti-CD28 bispecific antibody, without triggering a cytokine release syndrome (CRS) of grade 3 or higher according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.

2. The method of claim 1, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously, and wherein the combination dose of the isolated anti-hK2 / anti- CD3 bispecific antibody is 0.5-1800 mg per administration, preferably 50-800 mg per administration, such as 75, 100, 150 or 300 mg per administration, particularly 75, 150 or 300 mg per administration.

3. The method of claim 1 or claim 2, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, such as by subcutaneous injection or infusion, preferably by subcutaneous injection (e.g., one or more subcutaneous injection shots performed simultaneously or successively on the same day, as might be required to administer the total quantity of the (or each) combination dose).

4. The method of claim 3, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 0.5-2000 mg per administration, preferably 1.5-350 mg per administration, preferably 1.5-300 mg per administration, preferably 1.5-200 mg per administration, preferably 1.5-100 mg per administration, such as 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1.5, 4.5, 15, 45 or 90 mg per administration.

5. The method of any one of claims 1-4, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered intravenously.

6. The method of claim 5, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 0.5-1800 mg per administration, preferably 0.5-350 mg per administration, preferably 0.5-300 mg per administration, preferably 0.5-200 mg per administration, preferably 0.5-100 mg per administration, such as 0.5, 1, 1.5, 3, 4.5, 15, 30, 45, 90, or 100 mg per administration, particularly 1, 1.5, 4.5, 15, 45 or 90 mg per administration.

7. The method of claim 1, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration.

8. The method of claim 7, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific is 75 mg, 100 mg, 150 mg or 300 mg, preferably 75 mg, 150 mg or 300 mg, per administration; and the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is 1.5, 4.5, 15, 45 or 90 mg per administration.

9. The method of any of the foregoing claims, wherein the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti-hK2 / anti- CD3 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time).

10. The method of any of the foregoing claims, wherein the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered one or more times, for example 1, 2 or 3 times, in the same subject, preferably the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody is administered more than one time, for example 2 or 3 times, preferably 3 times in the same subject (e.g., on different days, for example the same combination dose level is administered 2 times on 2 different days, or 3 times on 3 different days, where the 2 or 3 different days are preferably spaced apart by at least one week time).

11. The method of any of the foregoing claims, wherein the combination dose of the isolated anti-hK2 / the anti-CD3 bispecific antibody and the combination dose of the isolated anti- PSMA / anti-CD28 bispecific antibody are administered on the same day, preferably, the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody is administered within 1-3 hours, such as within 1 hour, 2 hours or 3 hours, after the end of the administration of the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody.

12. The method of any of the foregoing claims, further comprising administering to the subject an initial treatment dose of 0.5-2000 mg per administration, preferably 0.5-1800 mg peradministration, preferably 50- 800 mg per administration, such as 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, particularly 75, 100, 150, 200, 300, 400 or 800 mg per administration, more particularly 75, 150, 200, 300 or 400 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of claim 1, preferably 5-10 days, such as 5, 6, 7, 8, 9, or 10 days, prior to the administering step (1) of claim 1.

13. The method of claim 12, wherein the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is of the same dose level as the combination dose of this antibody or is lower than the combination dose of this antibody.

14. The method of claim 12 or 13, wherein the initial treatment dose of the isolated anti- hK2 / anti-CD3 antibody is 50, 75, 100, 150, 200, 300, 400, 500, 600, 700 or 800 mg per administration, preferably 75, 150, 200 or 300 or 400 mg per administration, preferably 200 or 400 mg per administration, preferably 400 mg per administration.

15. The method of claim 14, wherein the initial treatment dose of the isolated anti-hK2 / anti-CD3 antibody is 75, 100, 150 or 300 mg per administration, the combination dose of this antibody is 75, 100, 150 or 300 mg per administration respectively, and wherein the isolated anti- hK2 / anti-CD3 antibody is administered intravenously.

16. The method of any one of claims 12-15, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered subcutaneously, preferably by subcutaneous injection or infusion, preferably by subcutaneous injection, or wherein the isolated anti-PSMA / anti-CD28 bispecific antibody is administered is administered intravenously.

17. The method of any of the foregoing claims, further comprising administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administering step (1) of claim 1, wherein the step-up doses are not higher than the combination dose of this antibody.

18. The method of any one of claims 12-15, further comprising administering to the subject one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody prior to the administration of the initial treatment dose, wherein the step-up doses are not higher than the initial treatment dose.

19. The method of claim 17 or claim 18, comprising administering to the subject a step-up dose of 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg peradministration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, prior to the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the initial treatment dose.

20. The method of any one of claims 17-19, comprising administering to the subject a first step- up dose and a second step-up dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the first step-up dose is administered prior to the second step-up dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administration of the second step-up dose, and wherein the second step-up dose is administered prior to the administering step (1) of claim 1 or the administration of the initial treatment dose, preferably 3-8 days, such as 3, 4, 5, 6, 7, or 8 days, prior to the administering step (1) of claim 1 or the administration of the initial treatment dose.

21. The method of any one of claims 17-20, wherein the first step-up dose is 2-5 mg per administration, such as 2, 2.5, 3, 3.5, 4, 4.5 or 5 mg per administration, preferably 3.5 mg per administration, of the isolated anti-hK2 / anti-CD3 bispecific antibody, and wherein the second step-up dose is 15-25 mg per administration, such as 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg per administration, preferably 18 mg per administration, of the isolated anti- hK2 / anti-CD3 bispecific antibody, preferably, the second step-up dose is administered prior to the administration of the initial treatment dose.

22. The method of any one of claims 17-21, wherein the one or more step-up doses of the isolated anti-hK2 / anti-CD3 bispecific antibody is administered intravenously.

23. The method of any one of the foregoing claims, further comprising administering to the subject one or more step-up doses of the isolated anti-PSMA / anti-CD28 bispecific antibody prior to the initial administration of the combination dose of the isolated anti-PSMA / anti- CD28 bispecific antibody, wherein the step-up doses are not higher than the combination dose of the isolated anti-PSMA / anti-CD28 bispecific antibody.

24. The method of any one of the foregoing claims, wherein the first antigen binding domain comprises a Fab.

25. The method of any one of the foregoing claims, wherein the second antigen binding domain comprises the VH2 of SEQ ID NO:18, and the VL2 of SEQ ID NO:

19.

26. The method of any one of the foregoing claims, wherein the second antigen binding domain comprises an scFv.

27. The method of any one of the foregoing claims, wherein the second antigen binding domain comprises an scFv that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO:

20.

28. The method of any one of the foregoing claims, wherein the first antigen binding domain comprises a Fab comprising a VH1 having the amino acid sequence of SEQ ID NO:10 and a VL1 having the amino acid sequence of SEQ ID NO:11; and wherein the second antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO:

20.

29. The method of any one of the foregoing claims, wherein the first antigen binding domain is linked to a first immunoglobulin (Ig) constant region or a fragment of the first Ig constant region and / or the second antigen binding domain is linked to a second immunoglobulin (Ig) constant region or a fragment of the second Ig constant region, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype.

30. The method of claim 29, wherein the first Ig constant region or the fragment of the first Ig constant region and / or the second Ig constant region or the fragment of the second Ig constant region is of an IgG1 isotype.

31. The method of claim 29 or claim 30, wherein the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprises at least one mutation that results in reduced binding of the anti- hK2 / anti-CD3 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat.

32. The method of claim 31, wherein the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof.

33. The method of any one of claims 29-32, wherein the first Ig constant region or the fragment of the first Ig constant region and the second Ig constant region or the fragment of the second Ig constant region comprise one or more heterodimerization mutations to promote heterodimerization.

34. The method of claim 33, wherein the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L andT394W, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V; or the first Ig constant region or the fragment of the first Ig constant region comprises the heterodimerization mutations T350V, L351Y, F405A and Y407V, and the second Ig constant region or the fragment of the second Ig constant region comprises the heterodimerization mutations T350V, T366L, K392L and T394W.

35. The method of any one of claims 29-34, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises a first heavy chain (HC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 21 and a first light chain (LC1) that is at least 90%, at least 95% or at least 100%, identical to the amino acid sequence of SEQ ID NO: 23, and a second heavy chain (HC2) that is at least 90%, 95% or 100% identical, to the amino acid sequence of SEQ ID NO:

24.

36. The method of claim 35, wherein the isolated anti-hK2 / anti-CD3 bispecific antibody comprises the HC1 having the amino acid sequence of SEQ ID NO: 21 or 22, the LC1 having the amino acid sequence of SEQ ID NO: 23 and the HC2 having the amino acid sequence of SEQ ID NO:

24.

37. The method of any one of the foregoing claims, wherein the third antigen binding domain comprises a Fab, and the fourth antigen binding domain comprises an scFv, preferably the scFv comprises one or more cysteine substitutions.

38. The method of any one of the foregoing claims, wherein the third antigen binding domain comprises a VH3 having the amino acid sequence of SEQ ID NO: 40 and a VL3 having the amino acid sequence of SEQ ID NO: 41; and the fourth antigen binding domain comprises an scFv having the amino acid sequence of SEQ ID NO:

47.

39. The method of any one of the foregoing claims, wherein the third antigen binding domain is linked to a third immunoglobulin (Ig) constant region or a fragment of the third Ig constant region, and / or the fourth antigen binding domain is linked to a fourth immunoglobulin (Ig) constant region or a fragment of the fourth Ig constant region, wherein the third Ig constant region or the fragment of the third Ig constant region and / or the fourth Ig constant region or the fragment of the fourth Ig constant region is of an IgG1, an IgG2, and IgG3 or an IgG4 isotype.

40. The method of claim 39, wherein one of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises heterodimerization mutation T366S, L368A and Y407V, wherein the residues are numbered according to the EU index of Kabat.

41. The method of claim 39 or claim 40, wherein the third and fourth Ig constant regions or the fragments thereof each comprise one or more mutations that result in reduced binding of the anti-PSMA / anti-CD28 bispecific antibody to a FcgR, such as one, two or three of the mutations of L234A, L235A and D265S, wherein the residues are numbered according to the EU index of Kabat.

42. The method of claim 41, wherein the FcgR is FcgRI, FcgRIIA, FcgRIIB or FcgRIII, or any combination thereof.

43. The method of any one of claims 39-42, wherein the third or fourth Ig constant regions or the fragment thereof further comprises purification mutations H435R and Y436F, wherein the residues are numbered according to the EU index of Kabat.

44. The method of any one of claims 39-43, wherein one of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / LT366W, and the other of the third and fourth Ig constant regions or the fragments thereof comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, wherein the residues are numbered according to the EU index of Kabat.

45. The method of any one of claims 39-44, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises a third heavy chain (HC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 44 and a third light chain (LC3) that is at least 90%, at least 95% or 100%, identical to the amino acid sequence of SEQ ID NO: 43, and a fourth heavy chain (HC4) that is at least 90%, at least 95% or 100% identical, to the amino acid sequence of SEQ ID NO:

42.

46. The method of claim 45, wherein the isolated anti-PSMA / anti-CD28 bispecific antibody comprises the HC3 having the amino acid sequence of SEQ ID NO: 44, the LC3 having the amino acid sequence of SEQ ID NO: 43 and the HC4 having the amino acid sequence of SEQ ID NO: 42.

47. The method of any of the foregoing claims, wherein the prostate cancer is advanced prostate cancer.

48. The method of any of the foregoing claims, wherein the prostate cancer is metastatic prostate cancer.

49. The method of any of the foregoing claims, wherein the prostate cancer is metastatic castration-resistant prostate cancer (mCRPC).

50. The method of any of the foregoing claims, wherein the prostate cancer is mCRPC with histologically confirmed adenocarcinoma of the prostate.

51. The method of any of the foregoing claims, wherein the prostate cancer is mCRPC with a prostate adenocarcinoma that has small cell or neuroendocrine (NE) features.

52. The method of any of the foregoing claims, wherein the prostate cancer is mCRPC with a prostate adenocarcinoma that does not comprise small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma.

53. The method of any of the foregoing claims, wherein the subject has received: at least one androgen receptor (AR)-targeted therapy, such as a treatment with abiraterone acetate plus prednisone, apalutamide, enzalutamide, or darolutamide, or at least one chemotherapy, such as a treatment with docetaxel; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody , or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody.

54. The method of any one of the foregoing claims, wherein the subject has received - orchiectomy or medical castration; or has received - androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), such as with leuprolide, goserelin, triptorelin, degarelix, or relugolic; prior to being administered with the combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody, or prior to being administered with the initial combination dose of the isolated anti-hK2 / anti-CD3 bispecific antibody.

55. The method of any of the foregoing claims, wherein no Adverse Event of grade 3 or higher (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0) is observed in the subject.

56. The method of any of the foregoing claims, wherein no event of Cytokine Release Syndrome (CRS) of Grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject.

57. The method of any of the foregoing claims, wherein no event of immune effector cell- associated neurotoxicity syndrome (ICANS) of grade 3 or higher (according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines) is observed in the subject.

58. The method of any of the foregoing claims, wherein no event of Injection Site Reaction (ISR) is observed in the subject.

59. The method of any of the foregoing claims, wherein no event of systemic Administration Related Reactions (sARRs) is observed in the subject.

60. The method of any of the foregoing claims, wherein no event of immune-related Adverse Event (irAE) is observed in the subject.

61. The method of any of the foregoing claims, wherein no event of hematologic toxicity of grade 3 or higher is observed in the subject.

62. The method of any of the foregoing claims, wherein no event of neutropenia of grade 3 or higher and no event of thrombocytopenia of Grade 3 or higher is observed in the subject, preferably no event of febrile neutropenia, no event of Grade 4 neutropenia for more than 7 days, no event of Grade 3 thrombocytopenia with clinically significant bleeding, and no event of Grade 4 thrombocytopenia with a duration of more than 7 days.

63. The method of any of the foregoing claims, wherein no event of non-hematological toxicity of Grade 3 or higher is observed in the subject.

64. The method of any of the foregoing claims, wherein no event of the following non- hematological toxicity is observed in the subject: - Grade 3 fatigue or asthenia; - Grade 3 fever; - Grade 3 nausea or grade 3 diarrhea; - Grade 3 hypertension; - Grade 3 alkaline phosphatase or GGT increase; - Grade 3 lipase or amylase increase; - Grade 3 electrolyte abnormality;- Grade 3 Adverse Event of tumor flare; and - First occurrence of a Grade 3 event of CRS, sARR or IRR.

65. The method of any of the foregoing claims, wherein no event of non-hematologic toxicity of grade 3 or higher and no event of hematologic toxicity of grade 3 or higher is observed in the subject.

66. The method of any of the foregoing claims, wherein no event of increase in aspartate aminotransferase (AST) or alkaline phosphatase (ALT) above 8 times the Upper Limit of Normal (ULN) is observed in the subject, or wherein no event of increase in AST or ALT above 5 times the ULN for more than 14 days is observed in the subject, or wherein no event of compliance with the Hy’Law criteria is observed in the subject (wherein the Hy’s law criteria are defined as ALT or AST value >3x ULN, and total bilirubin >2x ULN, and ALP <2x ULN, with no alternative etiology).

67. The method of any of the foregoing claims, which does not induce a Dose Limiting Toxicity (DLT) in the subject.

68. The method of any of the foregoing claims, wherein the probability that the DLT rate exceeds 30% in a cohort of at least 6 subjects, preferably in a cohort of 60-80 subjects, is lower than 95%.

69. The method of claim 67 or 68, wherein the DLT comprises one or more of the events of claims 61-68, preferably the events of claim 62 (hematological toxicity) and the events of claim 64 (non-hematological toxicity).

70. The method of any of the foregoing claims, which provides one or more events of improved efficacy chosen from among - increased T-cell activation; - increased T-cell infiltration into tumors; - improved T-cell mediated tumor killing; and - enhanced T-cell memory phenotypes; compared to prior to the administration of the isolated anti-hK2 / anti-CD3 bispecific antibody and of the isolated anti-PSMA / anti-CD28 bispecific antibody; or compared to the same method of treating prostate cancer, but without administration of the isolated anti-PSMA / anti-CD-28 bispecific antibody.

71. An isolated anti-hK2 / anti-CD3 bispecific antibody for use in the method of any of the foregoing claims.

72. An isolated anti-PSMA / anti-CD28 bispecific antibody for use in the method of any of claims 1-70.

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