Compositions targeting cancer antigens and methods of use thereof

Abstract

Disclosed herein are antibodies, antibody drug conjugates, and bispecific T cell engagers targeting TAS2R13, TMEM191C, ADAM20, or any combination thereof on the surface of cancer cells. Also disclosed are methods of using these compositions to treat cancer and / or slowing disease progression in a subject.

Description

COMPOSITIONS TARGETING CANCER ANTIGENS AND METHODS OF USE THEREOFI. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 642,873 filed 5 May 2024, which is incorporated herein in its entirety.II. REFERENCE TO THE SEQUENCE LISTING

[0002] The Sequence Listing submitted 5 May 2025 as an XML file named “24-3016-WO2_SL”, created on 5 May 2025 and having a size of 229,376 bytes is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52(e)(5).III. BACKGROUND

[0003] For decades, the foundations of cancer treatment have been surgery, chemotherapy, and radiation therapy. These continue to be critical mainstays of treatment, but new categories of treatment have recently helped transform the treatment picture for people with cancer. For example, it is highly desirable to exploit cancer-specific markers for therapeutic development.

[0004] Thus, there remains a need for treatment that is focused on therapy comprising antibodies, antibody drug conjugates, and bispecific T cell engagers. The compositions and methods disclosed herein meet this need.IV. BRIEF DESCRIPTION OF THE FIGURES

[0005] FIG. 1A shows mRNA expression in 125 metastases from 18 patients with SCLC. FIG. IB shows mRNA expression of TAS2R13 compared to CD19 in GTEX. FIG. 1C shows mRNA expression of TAS2R13 in human tumors in TCGA datasets.

[0006] FIG. 2A shows saining of >200 human tumors and heathy tissues using anti-TAS2R13 Ab#l including 3 different cancer cell lines (ovary, lung, and bladder). FIG. 2B shows flow cytometry for TAS2R13 #1 against 3 different cancer cell lines (A427, Calu6, and OvCar3). FIG. 2C shows staining of 4 healthy tissues.

[0007] FIG. 3 shows that CAR a[3 T cells co-stimulated with either CD28 or NKG2D effectively killed different tumor cells (e.g., OvCar3 (top), A427 (middle), and HCT116 (bottom)) as measured using the XCelligence system. The scFv was from TAS2R13 #1 (SEQ ID NO: 16).

[0008] FIG. 4A (A427 cells) and FIG. 4B (OvCar3) show that CAR y5 T cells transduced with the same constructs as the CAR a[3 T cells were more effective at killing different tumor cell lines in vitro. The scFv was from TAS2R13 #1 (SEQ ID NO: 16).

[0009] FIG. 5A (CAR a[3 T cells) and FIG. 5B (CAR y5 T cells) did not kill cultured primary hepatocytes (Clontech). The scFv is from TAS2R13 #1 (SEQ ID NO: 16).

[0010] FIG. 6A is a schematic of the experimental design while FIG. 6B (CAR a[3 T cells) and FIG. 6C (CAR y5 T cells) controlled the growth of established Calu 6 (lung) tumors in vivo. The scFv is from TAS2R13 #1 (SEQ ID NO: 16).

[0011] FIG. 7A is a schematic of the experimental design while FIG. 7B (CAR a[3 T cells) and FIG. 7C (CAR y5 T cells) controlled the growth of growth of established A427 (lung) tumors in vivo. The scFv is from TAS2R13 #1 (SEQ ID NO: 16).

[0012] FIG. 8A shows mRNA expression of ADAM20 in 125 metastases from 18 patients with SCLC. FIG. 8B shows the expression of ADAM20 in the Human Protein Atlas. FIG. 8C shows the mRNA level of ADAM20 in human tumors in TCGA datasets. FIG. 8D shows ADAM20 the mRNA level of ADAM 20 in GTEX.

[0013] FIG. 9A - FIG. 9F show that the anti-ADAM20 antibody “B5” specifically recognized A549 cells transduced with the ORF of ADAM20, but not mock-transduced A549 cells, which are ADAM20-negative.

[0014] FIG. 10A - FIG. 10D show mRNA expression of TMEM191C in 125 metastases from 18 patients with SCLC (FIG. 10A), GTEX (FIG. 10D), and the Human Protein Atlas (FIG. 10C). FIG. 10B shows expression of TMEM191C detected at the protein level using mass spectrometry (see J. Proteome Res. (2014) 13(6):2749-2760).

[0015] FIG. 11 shows flow cytometric analyses of the expression of ADAM20 (left panel) and TMEM191C (right panel) in different human cancer cell lines using the same Abs (on an IgGl backbone) conjugated to a fluorochrome.

[0016] FIG. 12A shows the guide tree cladogram of identified VH sequences for TMEM191C. The value indicates the genetic distance between two sequences: the lower the value, the closer the sequences. A value of zero indicates that the sequences are 100% identical. FIG. 12B shows the guide tree cladogram of identified VL sequences for TMEM191C. The value indicates the genetic distance between two sequences: the lower the value, the closer the sequences. A value of zero indicates that the sequences are 100% identical.

[0017] FIG. 13 shows 5 purified full-length recombinant human IgGs generated with the scFv sequences identified through phage display library panning, using a recombinant protein generated in CHO cells, consisting of the extracellular domain of human ADAM20 with [AA 30-691] and without [AA 207-691] pro-peptide (UniProt #043506) when screened those antibodies against cell lines known to express ADAM20 at the protein level or at the mRNA level (e.g., SKLU1) and other ADAM20-negative cells (e.g., A549). Based on this analysis, the sequence of IgG#C10, which produced differences for positive and negative cell lines. IgG#A2 and IgG#A7 recognizedTMEM191C and TAS2R13, respectively, and were used as additional controls (positive for Hela cells and negative for SKLU1 and A549 cells).

[0018] FIG. 14A- FIG. 14B shows AD AM20negA549 cells transduced with the AD AM20 ORF, the B5 clone reacted more strongly, compared to CIO, in 2 independent experiments. Based on these observations, clone B5 specifically recognized ADAM20.

[0019] FIG. 15A - FIG. 15C shows IHC for TMEM191C. FIG. 15A shows healthy colon, FIG. 15B shows healthy lung, and FIG. 15C shows healthy testis. Only healthy testis was positive for TMEM191C staining while healthy lung and healthy colon were negative (which matched mRNA expression as provided the Human Protein Atlas).

[0020] FIG. 16A - FIG. 16C shows IHC in healthy tissues for ADAM20. FIG. 16A shows healthy colon (negative for ADAM20), FIG. 16B shows healthy lung (negative for ADAM20), and FIG. 16C shows healthy testis (positive for ADAM20). FIG. 16D - FIG. 16F shows IHC in cancer tissues for ADAM20. FIG. 16E shows clear cell kidney cancer, FIG. 16E shows hepatocarcinoma, and FIG. 16F shows melanoma, all of which were positive for ADAM20 staining.V. BRIEF SUMMARY

[0021] Disclosed herein are anti-TAS2R13 antibodies. Disclosed herein are anti-TMEM191C antibodies. Disclosed herein are anti-ADAM20 antibodies. Disclosed herein are IgG antibodies recognizing TAS2R13-expressing cancer cells. Disclosed herein are IgG antibodies anti- TMEM191C-expressing cancer cells. Disclosed herein are IgG antibodies anti-ADAM20- expressing cancer cells. Disclosed herein are dimeric IgA antibodies recognizing TAS2R13- expressing cancer cells. Disclosed herein are dimeric IgA antibodies anti-TMEM191C- expressing cancer cells. Disclosed herein are dimeric IgA antibodies anti-ADAM20-expressing cancer cells.

[0022] Disclosed herein is an antibody comprising an IgG backbone, wherein the antibody recognizes a TAS2R13-expressing cancer cell. Disclosed herein is an antibody targeting TAS2R13-expressing cancer cells comprising an IgG backbone. Disclosed herein is an antibody comprising an IgG backbone, wherein the antibody recognizes a TMEM191C-expressing cancer cell. Disclosed herein is an antibody targeting TMEM191C-expressing cancer cells comprising an IgG backbone. Disclosed herein is an antibody comprising an IgG backbone, wherein the antibody recognizes a ADAM20-expressing cancer cell. Disclosed herein is an antibody targeting ADAM20-expressing cancer cells comprising an IgG backbone.

[0023] Disclosed herein are scFv (scFv) comprising antigen binding domains targeting antigens expressed on cancer cells. Disclosed herein are scFv comprising a TAS2R13 -antigen bindingdomain. Disclosed herein are scFv comprising a TMEM191C-antigen binding domain. Disclosed herein are scFv comprising a ADAM20-antigen binding domain.

[0024] Disclosed herein is an antibody drug conjugate comprising a disclosed antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed anti-TAS2R13 antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed anti-TMEM191C antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed anti-ADAM20 antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity.

[0025] Disclosed herein is an antibody drug conjugate comprising a disclosed IgG antibody recognizing TAS2R13-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed IgG antibody recognizing TMEM191C-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed IgG antibody recognizing ADAM20-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity.

[0026] Disclosed herein is an antibody drug conjugate comprising a disclosed dimeric IgA antibody recognizing TAS2R 13 -expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed dimeric IgA antibody recognizing TMEM191C-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed dimeric IgA antibody targeting ADAM20-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity.

[0027] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker. Bispecific T-cell engager molecules (BiTEs) constitute a class of bispecific single-chain antibodies for the polyclonal activation and redirection of cytotoxic T cells against pathogenic target cells (i.e., a cancer cell expressing TAS2R13, TMEM191C, or ADAM20).

[0028] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceuticalformulation thereof. Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof.

[0029] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0030] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0031] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate or a pharmaceutical formulation thereof. Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof.

[0032] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof. Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0033] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed. Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity, or a pharmaceutical formulation thereof.

[0034] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity, or a pharmaceutical formulation thereof.

[0035] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0036] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0037] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amountof a bispecific T cell engager (BiTE) comprising a disclosed scFv that binds to a TAS2R13- expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, or a pharmaceutical formulation thereof. Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of abispecific T cell engager (BiTE) comprising a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, or a pharmaceutical formulation thereof.

[0038] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising a disclosed scFv that binds to a TAS2R13- expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0039] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0040] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13- expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof.

[0041] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof.

[0042] Disclosed herein is a method of treating cancer, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0043] Disclosed herein is a method of slowing disease progression, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0044] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof a therapeutically effective amount of a disclosed antibody, a disclosed ADC, a disclosed BiTE, or a pharmaceutical formulation thereof.

[0045] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof.

[0046] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0047] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate or a pharmaceutical formulation thereof.

[0048] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subjectin need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0049] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity, or a pharmaceutical formulation thereof.

[0050] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a disclosed antibody drug conjugate comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

[0051] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20- expressing cancer cell, or a pharmaceutical formulation thereof.

[0052] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20- expressing cancer cell, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed. Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific Tcell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof.

[0053] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20- expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof.

[0054] Disclosed herein is a method of stimulating an effector cell mediated immune modulator response, the method comprising treating a subject in need thereof by administering to the subject in need thereof a therapeutically effective amount of a bispecific T cell engager (BiTE) comprising(i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20- expressing cancer cell, and (ii) a scFv that binds to a T cell marker, or a pharmaceutical formulation thereof, wherein, following the administering step, (i) the subject’s cancer is treated,(ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.VI. DETAILED DESCRIPTION

[0055] The present disclosure describes formulations, compounded compositions, kits, capsules, containers, and / or methods thereof. It is to be understood that the inventive aspects of which are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described.

[0056] All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.A. Definitions

[0057] Before the present compounds, compositions, articles, systems, devices, and / or methods are disclosed and described, it is to be understood that they are not limited to specific syntheticmethods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described.

[0058] This disclosure describes inventive concepts with reference to specific examples. However, the intent is to cover all modifications, equivalents, and alternatives of the inventive concepts that are consistent with this disclosure.

[0059] As used in the specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise.

[0060] The phrase “consisting essentially of’ limits the scope of a claim to the recited components in a composition or the recited steps in a method as well as those that do not materially affect the basic and novel characteristic or characteristics of the claimed composition or claimed method. The phrase “consisting of’ excludes any component, step, or element that is not recited in the claim. The phrase “comprising” is synonymous with “including”, “containing”, or “characterized by”, and is inclusive or open-ended. “Comprising” does not exclude additional, unrecited components or steps.

[0061] In an aspect, when referring to any numerical value, the term “about” means a value falling within a range that is ± 10% of the stated value.

[0062] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, a further aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms a further aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0063] References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight component X and 5parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound.

[0064] In an aspect, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. In an aspect, a disclosed method can optionally comprise one or more additional steps, such as, for example, repeating an administering step or altering an administering step.

[0065] In an aspect, “operably linked” refers to a juxtaposition where the components described are in a relationship permitting them to function in their intended manner. For example, a control element “operably linked” to a functional element is associated in such a way that expression and / or activity of the functional element is achieved under conditions compatible with the control element. In an aspect, a promotor is operably linked to nucleic acids.

[0066] In an aspect, the term “subject” refers to the target of administration, e.g., a human being. The term “subject” also includes domesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), and laboratory animals (e.g., mouse, rabbit, rat, guinea pig, fruit fly, etc.). Thus, the subject can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Alternatively, the subject of the herein disclosed methods can be a human, nonhuman primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex, and thus, adult and child subjects, as well as fetuses, whether male or female, are intended to be covered. In an aspect, a subject can be a human patient. In an aspect, a subject can have cancer, be suspected of having cancer, or be at risk of developing cancer.

[0067] In an aspect, the term “diagnosed” means having been subjected to an examination by a person of skill, for example, a physician, and found to have a condition that can be diagnosed or treated by one or more disclosed ABs, one or more ADCs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof, or by one or more of the disclosed methods. For example, “diagnosed with a disease or disorder” means having been subjected to an examination by a person of skill, for example, a physician, and found to have a condition (such as cancer) that can be treated by one or more disclosed ABs, one or more ADCs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof, or by one or more of the disclosed methods. For example, “suspected of having a disease or disorder” can mean having been subjected to an examination by a person of skill, for example, a physician, and found to have a condition (such as cancer) that can likely be treated by one or more disclosed ABs, one or more ADCs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or moredisclosed pharmaceutical formulations, or any combination thereof, or by one or more of the disclosed methods. In an aspect, an examination can be physical, can involve various tests (e.g., blood tests, genotyping, biopsies, etc.), scans (e.g., CT scans, PET scans, etc.), and assays (e.g., enzymatic assay), or a combination thereof.

[0068] TAS2R13 (Taste 2 Receptor Member 13) is a gene product that belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. TAS2R13 can be identified as HGNC 14919, NCBI Gene 50838, Ensembl ENSG00000212128, OMIM 604792, and UniProtKB / Swiss-Prot Q9NYV9.

[0069] TMEM191C (Transmembrane Protein 191C) is a protein coding gene. Diseases associated with TMEM191C include Glioma Susceptibility 1. TMEM191C can be identified as HGNC 33601, NCBI Gene 645426, Ensembl ENSG00000206140, and UniProtKB / Swiss-Prot A6NGB0.

[0070] ADAM20 (ADAM Metallopeptidase Domain 20) encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The expression of this gene is testis-specific. ADAM20 can be identified as HGNC 199, NCBI Gene 8748, Ensembl ENSG00000134007, OMIM 603712, and UniProtKB / Swiss-Prot 043506.

[0071] A “patient” refers to a subject afflicted with a disease or disorder (e.g., cancer). In an aspect, a patient can refer to a subject that has been diagnosed with or is suspected of having a disease or disorder such as cancer. In an aspect, a patient can refer to a subject that has been diagnosed with or is suspected of having a disease or disorder and is seeking treatment or receiving treatment for a disease or disorder (such as cancer).

[0072] In an aspect, the phrase “identified to be in need of treatment for a disease or disorder,” or the like, refers to selection of a subject based upon need for treatment of the disease or disorder. For example, a subject can be identified as having a need for treatment of a disease or disorder (e.g., cancer) based upon an earlier diagnosis by a person of skill and thereafter subjected to treatment for the cancer. In an aspect, the identification can be performed by a person different from the person making the diagnosis. In an aspect, the administration can be performed by one who performed the diagnosis.

[0073] In an aspect, “activated” and “activation” can refer to the state of a T cell that has been sufficiently stimulated to induce detectable cellular proliferation. Activation can also be associated with induced cytokine production and detectable effector functions. The term“activated T cells” can refer to T cells that are proliferating. Signals generated through the TCR alone may be insufficient for full activation of the T cell and one or more secondary or costimulatory signals may also be required. Thus, T cell activation comprises a primary stimulation signal through the TCR / CD3 complex and one or more secondary costimulatory signals. Costimulation can be evidenced by proliferation and / or cytokine production by T cells that have received a primary activation signal, such as stimulation through the TCR / CD3 complex.

[0074] In an aspect, “inhibit,” “inhibiting”, and “inhibition” mean to diminish or decrease an activity, level, response, condition, severity, disease, or other biological parameter. This can include, but is not limited to, the complete ablation of the activity, level, response, condition, severity, disease, or other biological parameter. This can also include, for example, a 10% inhibition or reduction in the activity, level, response, condition, severity, disease, or other biological parameter as compared to the native or control level (e.g., a subject not receiving one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof). Thus, in an aspect, the inhibition or reduction can be a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any amount of reduction in between as compared to native or control levels. In an aspect, the inhibition or reduction can be 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100% as compared to a native or control level (e.g., a subject not receiving one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof). In an aspect, the inhibition or reduction can be 0-25%, 25-50%, 50-75%, or 75-100% as compared to native or control levels. In an aspect, a native or control level can be a pre-disease or pre-disorder level (such as a precancer state).

[0075] The words “treat” or “treating” or “treatment” include palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. In an aspect, the terms cover any treatment of a subject, including a mammal e.g., a human), and includes: (i) preventing the undesired physiological change, disease, pathological condition, or disorder from occurring in a subject that can be predisposed to the disease but has not yet been diagnosed as having it; (ii) inhibiting the physiological change, disease, pathological condition, or disorder, i.e., arresting its development; or (iii) relieving the physiological change,disease, pathological condition, or disorder, i.e., causing regression of the disease. For example, in an aspect, treating a disease or disorder can reduce the severity of an established a disease or disorder in a subject by 1%-100% as compared to a control (such as, for example, an individual not having cancer). In an aspect, treating can refer to a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of a disease or disorder (such as cancer). For example, treating a disease or disorder can reduce one or more symptoms of a disease or disorder in a subject by 1%- 100% as compared to a control (such as, for example, an individual not having cancer). In an aspect, treating can refer to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% reduction of one or more symptoms of an established a disease or disorder (e.g., cancer). It is understood that treatment does not necessarily refer to a cure or complete ablation or eradication of a disease or disorder. However, in an aspect, treatment can refer to a cure or complete ablation or eradication of a disease or disorder (such as cancer).

[0076] In an aspect, the term “prevent” or “preventing” or “prevention” refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit, or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. In an aspect, preventing a disease or disorder having chromatin deregulation and / or chromatin dysregulation is intended. The words “prevent”, “preventing”, and “prevention” also refer to prophylactic or preventative measures for protecting or precluding a subject (e.g., an individual) not having a given a disease or disorder (such as cancer) or related complication from progressing to that complication. In an aspect, preventing metastasis is intended.

[0077] In an aspect, the terms “administering” and “administration” refer to any method of providing one or more of the disclosed interfering molecules, the disclosed anti-PDl molecules, the disclosed pharmaceutical formulations, or a combination thereof to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, the following: oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, in utero administration, intra-tumoral administration, intrahepatic administration, intravaginal administration, ophthalmic administration, intra-aural administration, otic administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-CSF administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can also include hepatic intraarterial administration or administration through the hepatic portal vein (HPV). Administrationof a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immune modulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof can comprise administration directly into the CNS or the PNS. Administration can be continuous or intermittent. Administration can comprise a combination of one or more routes.

[0078] By “determining the amount” is meant both an absolute quantification of a particular analyte (e.g., biomarker for cancer, for example) or a determination of the relative abundance of a particular analyte (e.g., a cancer biomarker). The phrase includes both direct or indirect measurements of abundance or both.

[0079] In an aspect, the term “pharmaceutically acceptable carrier” refers to sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. In an aspect, a pharmaceutical carrier employed can be a solid, liquid, or gas. In an aspect, examples of solid carriers can include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. In an aspect, examples of liquid carriers can include sugar syrup, peanut oil, olive oil, and water. In an aspect, examples of gaseous carriers can include carbon dioxide and nitrogen. In preparing a disclosed composition for oral dosage form, any convenient pharmaceutical media can be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like can be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like can be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets can be coated by standard aqueous or nonaqueous techniques. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. It can alsobe desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. Desirably, at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers.

[0080] In an aspect, the term “excipient” refers to an inert substance which is commonly used as a diluent, vehicle, preservative, binder, or stabilizing agent, and includes, but is not limited to, proteins (e.g., serum albumin, etc.), amino acids (e.g., aspartic acid, glutamic acid, lysine, arginine, glycine, histidine, etc.), fatty acids and phospholipids (e.g., alkyl sulfonates, caprylate, etc.), surfactants (e.g., SDS, polysorbate, nonionic surfactant, etc.), saccharides (e.g., sucrose, maltose, trehalose, etc.) and polyols (e.g., mannitol, sorbitol, etc.). See, also, for reference, Remington’s Pharmaceutical Sciences, (1990) Mack Publishing Co., Easton, Pa., which is hereby incorporated by reference in its entirety.

[0081] In an aspect, “concurrently” means (1) simultaneously in time, or (2) at different times during the course of a common treatment schedule.

[0082] In an aspect, “contacting” refers to bringing one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof together with a target area or intended target area in such a manner that one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof can exert an effect on the intended target or targeted area either directly or indirectly. A target area or intended target area can be one or more of a subject’s organs (e.g., lungs, heart, liver, kidney, brain, etc.) hosting cancerous cells expressing TAS2R13, TMEM191C, and / or ADAM20. In an aspect, a target area or intended target area can be any cell or any organ infected by a disease or disorder (such as cancer). In an aspect, a target area or intended target area can be any organ, tissue, or cells that are affected by a disease or disorder (such as cancer).

[0083] In an aspect, “determining” can refer to measuring or ascertaining the presence and severity of a disease or disorder, such as, for example, cancer or cancer cells expressing TAS2R13, TMEM191C, and / or ADAM20. Methods and techniques used to determine the presence and / or severity of a disease or disorder are typically known to the medical arts. For example, the art is familiar with the ways to identify and / or diagnose the presence, severity, or both of a disease or disorder (such as, for example, cancer).

[0084] In an aspect, “effective amount” and “amount effective” can refer to an amount that is sufficient to achieve the desired result such as, for example, the treatment and / or prevention of a disease or disorder (e.g., a cancer) or a suspected disease or disorder. In an aspect, the terms “effective amount” and “amount effective” can refer to an amount that is sufficient to achieve the desired an effect on an undesired condition e.g., a cancer). For example, a “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms, but is generally insufficient to cause adverse side effects. In an aspect, “therapeutically effective amount” means an amount of a disclosed nucleic acid molecule, a disclosed vector, a disclosed cell, or a disclosed pharmaceutical formulation; that (i) treats the particular disease, condition, or disorder (e.g., a cancer), (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder e.g., cancer), or (iii) delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein (e.g., cancer). The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof, employed; the disclosed methods employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof employed; the duration of the treatment; drugs used in combination or coincidental with the one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof employed, and other like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of the one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, then the effective daily dose can be divided into multipledoses for purposes of administration. Consequently, a single dose of one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof can contain such amounts or submultiples thereof to make up the daily dose. The dosage can be adjusted by the individual physician in the event of any contraindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. In further various aspects, a preparation can be administered in a “prophylactically effective amount”; that is, an amount effective for prevention of a disease or condition, such as, for example, a disease or disorder due to a missing, deficient, and / or mutant protein or enzyme.

[0085] In an aspect, polynucleotide or nucleic acid can be used interchangeably, and refer to polymers of nucleotides of any length and includes DNA and RNA. In an aspect, nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthetic reaction. In an aspect, a polynucleotide can comprise modified nucleotides, such as methylated nucleotides and their analogs. Unless specified otherwise, the left-hand end of any single- stranded polynucleotide sequence disclosed herein is the 5’ end; the left-hand direction of double-stranded polynucleotide sequences is referred to as the 5’ direction. The direction of 5’ to 3’ addition of nascent RNA transcripts is referred to as the transcription direction; sequence regions on the DNA strand having the same sequence as the RNA transcript that are 5’ to the 5’ end of the RNA transcript are referred to as “upstream sequences” ; sequence regions on the DNA strand having the same sequence as the RNA transcript that are 3’ to the 3’ end of the RNA transcript are referred to as “downstream sequences”.

[0086] The term “antibody” (Ab) includes, without limitation, a glycoprotein immunoglobulin that binds specifically to an antigen. An antibody can comprise at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, or an antigen-binding molecule thereof. Each H chain can comprise a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region can comprise three constant domains, CHI, CH2 and CH3. Each light chain can comprise a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region can comprise one constant domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL can comprise three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order:FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions of the heavy and light chains can contain a binding domain that interacts with an antigen. The constant regions of the Abs can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. Generally, human antibodies can be approximately 150 kD tetrameric agents composed of two identical heavy (H) chain polypeptides (about 50 kD each) and two identical light (L) chain polypeptides (about 25 kD each) that associate with each other into what is commonly referred to as a “Y-shaped” structure. The heavy and light chains can be linked or connected to one another by a single disulfide bond and two other disulfide bonds can connect the heavy chain hinge regions to one another, so that the dimers can be connected to one another and the tetramer can be formed. Naturally produced antibodies are also glycosylated, e.g., on the CH2 domain. The term “antibody” is used to mean an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing etc., through at least one antigen recognition site within the variable region of the immunoglobulin molecule. In an aspect, the term encompasses intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab', F(ab')2, and Fv fragments), single chain Fv (scFv) mutants, multispecific antibodies such as bispecific antibodies generated from at least two intact antibodies, fusion proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen recognition site so long as the antibodies exhibit the desired biological activity. An antibody can be of any the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2), based on the identity of their heavy-chain constant domains referred to as alpha, delta, gamma, epsilon, and mu, respectively. The different classes of immunoglobulins have different and well-known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated to other molecules such as toxins, radioisotopes, etc. In an aspect, any disclosed antibody can be humanized. Antibody humanization is the process of replacing non-human antibody frameworks with human ones. Successful antibody humanization depends on maintaining the affinity after replacing residues. In an aspect, humanized antibodies can be antibody molecules in which at least part of the sequence of both the light chain and the heavy chain arise from human genes. Such antibodies are termed “humanized antibodies”, “human antibodies”, or “fully human antibodies” herein.

[0087] In an aspect, a single-chain antibody (scFv) is a genetically engineered molecule containing the VH and VL domains of one or more antibody (ies) linked by a suitable polypeptide linker as a genetically fused single chain molecule. The intramolecular orientation of the VH-domain and the VL-domain in a scFv, is typically not decisive for scFvs. Thus, scFvs with both possible arrangements (VH-domain-linker domain- VL-domain; VL-domain-linker domain- VH- domain) can be used.

[0088] The term “variable region” or “variable domain” is used interchangeably. The variable region typically refers to a portion of an antibody, generally, a portion of a light or heavy chain, typically about the amino-terminal 110 to 120 amino acids in the mature heavy chain and about 90 to 115 amino acids in the mature light chain, which differ extensively in sequence among antibodies and are used in the binding and specificity of a particular antibody for its particular antigen. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). In an aspect, the variable region comprises rodent or murine CDRs and human framework regions (FRs). In an aspect, the variable region is a primate (e.g., non-human primate) variable region. In an aspect, the variable region comprises rodent or murine CDRs and primate framework regions (FRs).

[0089] The terms “VL” and “VL domain” are used interchangeably to refer to the light chain variable region of an antibody or an antigen-binding molecule thereof. The terms “VH” and “VH domain” are used interchangeably to refer to the heavy chain variable region of an antibody or an antigen-binding molecule thereof.

[0090] The terms “constant region” and “constant domain” are interchangeable and have a meaning common in the art. The constant region is an antibody portion, e.g., a carboxyl terminal portion of a light and / or heavy chain which is not directly involved in binding of an antibody to antigen but which can exhibit various effector functions, such as interaction with the Fc receptor. The constant region of an immunoglobulin molecule generally has a more conserved amino acid sequence relative to an immunoglobulin variable domain.

[0091] The term “heavy chain” when used in reference to an antibody can refer to any distinct type, e.g., alpha (a), delta (5), epsilon (a), gamma (y) and mu (p), based on the amino acid sequence of the constant domain, which give rise to IgA, IgD, IgE, IgG and IgM classes of antibodies, respectively, including subclasses of IgG, e.g., IgGi, IgG?, IgGs and IgG4.

[0092] The term “light chain” when used in reference to an antibody can refer to any distinct type, e.g., kappa (K) or lambda (A) based on the amino acid sequence of the constant domains. Light chain amino acid sequences are well known in the art. In an aspect, the light chain is a human light chain.

[0093] “Endogenous” with reference to a gene, protein, and / or nucleic acid refers to the natural presence of that gene, protein, and / or nucleic acid in a cell, such as an immune cell. “Exogenous”refers to an introduced agent, such as a nucleic acid, gene, or protein, into a cell, for example from an outside source. A nucleic acid introduced into a cell is exogenous even if it encodes a protein which is naturally found in the cell. Such exogenous introduction of a nucleic acid encoding a protein can be used to increase the expression of the protein over the level that would naturally be found in the cell under similar conditions, e.g., without introduction of the exogenous nucleic acid.

[0094] In an aspect, “T cell receptor” or “TCR” refers to antigen-recognition molecules present on the surface of T cells. During normal T cell development, each of the four TCR genes can rearrange leading to highly diverse TCR proteins.

[0095] In an aspect, “effector function” can refer to a biological result of interaction of an antibody Fc region with an Fc receptor or ligand. Effector functions comprise, without limitation, antibodydependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and complement mediated cytotoxicity (CMC). An effector function may be antigen binding dependent, antigen binding independent, or both. ADCC refers to lysis of antibody -bound target cells by immune effector cells. ADCC is generally understood to involve Fc receptor (FcR)- bearing effector cells recognizing and subsequently killing antibody-coated target cells (e.g., cells that express on their surface antigens to which an antibody is bound). Effector cells that mediate ADCC may comprise immune cells, comprising yet not limited to, one or more of natural killer (NK) cells, macrophages, neutrophils, eosinophils.

[0096] The term “immunotherapy” refers to the treatment of a subject afflicted with, or at risk of contracting or suffering a recurrence of, a disease by a method comprising inducing, enhancing, suppressing or otherwise modifying an immune response. Examples of immunotherapy can include, but are not limited to, NK cells and T cell therapies. T cell therapy can include adoptive T cell therapy, tumor-infiltrating lymphocyte (TIL) immunotherapy, autologous cell therapy, engineered autologous cell therapy (eACTTM), and allogeneic T cell transplantation (e.g., cells expressing CARs targeting TAS2R13, TMEM191C, and / or ADAM20). However, one of skill in the art would recognize that the conditioning methods disclosed herein would enhance the effectiveness of any transplanted T cell therapy.

[0097] In an aspect, T cells or NK cells can come from any source known in the art. For example, T cells and NK cells can be differentiated in vitro from a hematopoietic stem cell population (for example iPSCs) or can be obtained from a subject. T cells and NK cells can be obtained from, e.g., peripheral blood mononuclear cells (PBMCs), bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and tumors. In addition, the T cells can be derived from one or more T cell lines available in the art. T cellscan also be obtained from a unit of blood collected from a subject using any number of techniques known to the skilled artisan.

[0098] In an aspect, the term “antibody fragment” refers to a portion of an intact antibody and refers to the antigenic determining variable regions of an intact antibody. Examples of antibody fragments include, but are not limited to Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, single chain antibodies, and multi-specific antibodies formed from antibody fragments.

[0099] In an aspect, “monoclonal antibody” refers to homogenous antibody population involved in the highly specific recognition and binding of a single antigenic determinant, or epitope. The term “monoclonal antibody” encompasses both intact and full-length monoclonal antibodies as well as antibody fragments (such as Fab, Fab', F(ab')2, Fv), single chain (scFv) mutants, fusion proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen recognition site. Furthermore, “monoclonal antibody” refers to such antibodies made in any number of manners including, but not limited to, by hybridoma, phage selection, recombinant expression, and transgenic animals.

[0100] In an aspect, the term “humanized antibody” refers to forms of non-human (e.g., murine) antibodies that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human sequences. Typically, humanized antibodies are human immunoglobulins in which residues from the complementary determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g., mouse, rat, rabbit, hamster, etc.) that have the desired specificity, affinity, and capability. In some instances, the Fv framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody from a non-human species that has the desired specificity, affinity, and capability. The humanized antibody can be further modified by the substitution of additional residue either in the Fv framework region and / or within the replaced non-human residues to refine and optimize antibody specificity, affinity, and / or capability. In general, the humanized antibody will comprise substantially all of at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin.

[0101] That an antibody “selectively binds” or “specifically binds” to an epitope or receptor means that the antibody reacts or associates more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of the above to the epitope or receptor than with alternative substances, including unrelated proteins. “Selectively binds” or “specifically binds”means, for instance, that an antibody binds to a protein with a KD of about 0.1 mM or less, more usually about 1 pM or less. “Selectively binds” or “specifically binds” means at times that an antibody binds to a protein with a KD of about 0.1 mM or less, at times about 1 pM or less, at times about 0.1 pM or less, at times about 0.01 pM or less, and at times about 1 nM or less. It is understood that, in an aspect, an antibody or binding moiety that specifically binds to a first target may or may not specifically bind to a second target. As such, “specific binding” does not necessarily require (although it can include) exclusive binding, e.g., binding to a single target. Thus, an antibody may, in an aspect, specifically bind to more than one target (e.g., human TAS2R13, TMEM191C, and / or ADAM20). In an aspect, the multiple targets may be bound by the same antigen-binding site on the antibody.

[0102] In an aspect, an “antigen” refers to a compound, composition, or substance that may stimulate the production of antibodies or a T cell response in a human or animal, including compositions (such as one that includes a tumor-specific protein) that are injected or absorbed into a human or animal. An antigen reacts with the products of specific humoral or cellular immunity, including those induced by heterologous antigens, such as the disclosed antigens. A “target antigen” is an antigen that is not substantially found on the surface of other normal (desired) cells and to which a binding domain of disclosed TCR or disclosed CAR can bind (e.g. TAS2R13, TMEM191C, and / or ADAM20 on cancer cells).

[0103] In an aspect, a “target” expressing TAS2R13, TMEM191C, or ADAM20 can bind to a disclosed binding motif, a disclosed CAR, a disclosed antibody, a disclosed scFv, a disclosed ADC, a disclosed BiTE, or a disclosed antigen binding agent.

[0104] In an aspect, the term “antibody production” can have both general and specific meanings. In the broad sense, it can refer to the entire process of creating a usable specific antibody, including steps of immunogen preparation, immunization, hybridoma creation, collection, screening, isotyping, purification, and labeling for direct use in a particular method. In the more restricted sense, antibody production refers to the steps leading up to antibody generation but does not include various forms of purifying and labeling the antibody for particular uses. Antibody production involves preparation of antigen samples and their safe injection into laboratory or farm animals to evoke high expression levels of antigen-specific antibodies in the serum, which can then be recovered from the animal. Polyclonal antibodies are recovered directly from serum (bleeds). Monoclonal antibodies are produced by fusing antibody-secreting spleen cells from immunized mice with immortal myeloma cell to create monoclonal hybridoma cell lines that express the specific antibody in cell culture supernatant. Successful antibody production depends upon careful planning and implementation with respect to several important steps andconsiderations: (i) synthesize or purify the target antigen (e.g., peptide or hapten); (ii) choose an appropriate immunogenic carrier protein; (iii) conjugate the antigen and carrier protein to create the immunogen; immunize animals using appropriate schedule and adjuvant formula; and screen serum (or hybridoma) for antibody titer and isotype (also called antibody characterization).

[0105] In an aspect, the terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals in which a population of cells are characterized by unregulated cell growth. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia. More particular examples of such cancers include squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.

[0106] In an aspect, the terms “proliferative disorder” and “proliferative disease” refer to disorders associated with abnormal cell proliferation such as cancer.

[0107] In an aspect, “tumor” and “neoplasm” refer to any mass of tissue that result from excessive cell growth or proliferation, either benign (noncancerous) or malignant (cancerous) including pre- cancerous lesions. “Metastasis” refers to the process by which a cancer spreads or transfers from the site of origin to other regions of the body with the development of a similar cancerous lesion at the new location. A “metastatic” or “metastasizing” cell is one that loses adhesive contacts with neighboring cells and migrates via the bloodstream or lymph from the primary site of disease to invade neighboring body structures.

[0108] The terms “cancer stem cell” or “tumor stem cell” or “solid tumor stem cell” are used interchangeably herein and refer to a population of cells from a solid tumor that: (1) have extensive proliferative capacity; (2) are capable of asymmetric cell division to generate one or more kinds of differentiated progeny with reduced proliferative or developmental potential; and (3) are capable of symmetric cell divisions for self-renewal or self-maintenance. These properties of “cancer stem cells” or “tumor stem cells” or “solid tumor stem cells” confer on those cancer stem cells the ability to form palpable tumors upon serial transplantation into an immunocompromised mouse compared to the majority of tumor cells that fail to form tumors. Cancer stem cells undergo self-renewal versus differentiation in a chaotic manner to form tumors with abnormal cell types that can change over time as mutations occur.

[0109] In an aspect, “cancer cell” or “tumor cell” and grammatical equivalents refer to the total population of cells derived from a tumor including both non-tumorigenic cells, which comprise the bulk of the tumor cell population, and tumorigenic stem cells (cancer stem cells).

[0110] In an aspect, “tumorigenic” refers to the functional features of a solid tumor stem cell including the properties of self-renewal (giving rise to additional tumorigenic cancer stem cells) and proliferation to generate all other tumor cells (giving rise to differentiated and thus non- tumorigenic tumor cells) that allow solid tumor stem cells to form a tumor.

[0111] In an aspect, the “turn origeni city” of a tumor refers to the ability of a random sample of cells from the tumor to form palpable tumors upon serial transplantation into immunocompromised mice.

[0112] In an aspect, “lipid nanoparticles” or “LNPs” can deliver nucleic acid (e.g., DNA or RNA), protein (e.g., RNA-guided DNA binding agent), or nucleic acid together with protein. LNPs can comprise biodegradable, ionizable lipids. For example, LNPs can comprise (9Z,12Z)-3-((4,4- bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9,12-di enoate, also called 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl (9Z, 12Z)-octadeca-9, 12-di enoate) or another ionizable lipid. In an aspect, the term cationic and ionizable in the context of LNP lipids can be use interchangeably, e.g., wherein ionizable lipids are cationic depending on the pH.

[0113] In an aspect, “sequence identity” and “sequence similarity” can be determined by alignment of two peptide or two nucleotide sequences using global or local alignment algorithms. Sequences may then be referred to as “substantially identical” or “essentially similar” when they are optimally aligned. For example, sequence similarity or identity can be determined by searching against databases such as FASTA, BLAST, etc., but hits should be retrieved and aligned pairwise to compare sequence identity. Two proteins or two protein domains, or two nucleic acid sequences can have “substantial sequence identity” if the percentage sequence identity is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more, preferably 90%, 95%, 98%, 99% or more. Such sequences are also referred to as “variants” herein, e.g., other variants of a missing, deficient, and / or mutant protein or enzyme. It should be understood that sequence with substantial sequence identity do not necessarily have the same length and may differ in length. For example, sequences that have the same nucleotide sequence but of which one has additional nucleotides on the 3’- and / or 5’-side are 100% identical.

[0114] In an aspect, “immune-modulating” refers to the ability of a disclosed nucleic acid molecules, a disclosed vector, a disclosed pharmaceutical formulation, or a disclosed agent to alter (modulate) one or more aspects of the immune system. The immune system functions to protectthe organism from infection and from foreign antigens by cellular and humoral mechanisms involving lymphocytes, macrophages, and other antigen-presenting cells that regulate each other by means of multiple cell-cell interactions and by elaborating soluble factors, including lymphokines and antibodies, that have autocrine, paracrine, and endocrine effects on immune cells.

[0115] In an aspect, “immune modulator” refers to an agent that is capable of adjusting a given immune response to a desired level (e.g., as in immunopotentiation, immunosuppression, or induction of immunologic tolerance). Examples of immune modulators include but are not limited to, a disclosed immune modulator can comprise aspirin, azathioprine, belimumab, betamethasone dipropionate, betamethasone valerate, bortezomib, bredinin, cyazathioprine, cyclophosphamide, cyclosporine, deoxyspergualin, didemnin B, fluocinolone acetonide, folinic acid, ibuprofen, IL6 inhibitors (such as sarilumab) indomethacin, inebilizumab, intravenousy globulin (IVIG), methotrexate, methylprednisolone, mycophenolate mofetil, naproxen, prednisolone, prednisone, prednisolone indomethacin, rapamycin, rituximab, sirolimus, sulindac, synthetic vaccine particles containing rapamycin (SVP -Rapamycin or ImmTOR), thalidomide, tocilizumab, tolmetin, triamcinolone acetonide, anti-CD3 antibodies, anti-CD4 antibodies, anti-CD19 antibodies, anti- CD20 antibodies, anti-CD22 antibodies, anti-CD40 antibodies, anti-FcRN antibodies, anti-IL6 antibodies, anti -IGF 1R antibodies, an IL2 mutein, a BTK inhibitor, or a combination thereof. In an aspect, a disclosed immune modulator can comprise one or more Treg (regulatory T cells) infusions (e.g., antigen specific Treg cells to AAV). In an aspect, a disclosed immune modulator can be bortezomib or SVP -Rapamycin. In an aspect, an immune modulator can be administered by any suitable route of administration including, but not limited to, in utero, intra-CSF, intrathecally, intravenously, subcutaneously, transdermally, intradermally, intramuscularly, orally, transcutaneously, intraperitoneally (IP), or intravaginally. In an aspect, a disclosed immune modulator can be administered using a combination of routes. Administration can also include hepatic intra-arterial administration or administration through the hepatic portal vein (HPV). Administration of an immune modulator can be continuous or intermittent, and administration can comprise a combination of one or more routes.

[0116] In an aspect, the term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic products, that contain information about the indications, usage, dosage, administration, contraindications and / or warnings concerning the use of such therapeutic products.

[0117] In an aspect, the term “in combination” in the context of the administration of other therapies (e.g., other agents) includes the use of more than one therapy (e.g., drug therapy).Administration “in combination with” one or more further therapeutic agents includes simultaneous (e.g., concurrent) and consecutive administration in any order. The use of the term “in combination” does not restrict the order in which therapies are administered to a subject. By way of non-limiting example, a first therapy (e.g., one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof) can be administered prior to (e.g., 1 minute, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks), concurrently, or after (e.g., 1 minute, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks or longer) the administration of a second therapy to a subject having or diagnosed with cancer.

[0118] Disclosed are the components to be used to prepare the one or more disclosed ABs, one or more disclosed scFvs, or one or more disclosed BiTEs, one or more disclosed pharmaceutical formulations, or any combination thereof used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the invention. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific aspects or combination of aspects of the methods of the invention.B. Compositions for Use in the Disclosed Methods1. Antibodies

[0119] Disclosed herein are anti-TAS2R13 antibodies. Disclosed herein are anti-TMEM191C antibodies. Disclosed herein are anti-ADAM20 antibodies. Disclosed herein are IgG antibodies recognizing TAS2R13-expressing cancer cells. Disclosed herein are IgG antibodies anti- TMEM191C-expressing cancer cells. Disclosed herein are IgG antibodies anti-ADAM20- expressing cancer cells. Disclosed herein are dimeric IgA antibodies recognizing TAS2R13- expressing cancer cells. Disclosed herein are dimeric IgA antibodies anti-TMEM191C- expressing cancer cells. Disclosed herein are dimeric IgA antibodies anti-ADAM20-expressing cancer cells.

[0120] Disclosed herein are anti-TAS2R13 naked antibodies. Disclosed herein are anti- TMEM191C naked antibodies. Disclosed herein are anti-ADAM20 naked antibodies. Disclosed herein are naked IgG antibodies recognizing TAS2R13 -expressing cancer cells. Disclosed herein are naked IgG antibodies anti-TMEM191C-expressing cancer cells. Disclosed herein are naked IgG antibodies anti-ADAM20-expressing cancer cells. Disclosed herein are naked dimeric IgA antibodies recognizing TAS2R 13 -expressing cancer cells. Disclosed herein are naked dimeric IgA antibodies anti-TMEM191C-expressing cancer cells. Disclosed herein are naked dimeric IgA antibodies anti-ADAM20-expressing cancer cells.

[0121] Disclosed herein are anti-TAS2R13 conjugated antibodies. Disclosed herein are anti- TMEM191C conjugated antibodies. Disclosed herein are anti-ADAM20 conjugated antibodies. Disclosed herein are conjugated IgG antibodies recognizing TAS2R13-expressing cancer cells. Disclosed herein are conjugated IgG antibodies anti-TMEM191C-expressing cancer cells. Disclosed herein are conjugated IgG antibodies anti-ADAM20-expressing cancer cells. Disclosed herein are conjugated dimeric IgA antibodies recognizing TAS2R13-expressing cancer cells. Disclosed herein are conjugated dimeric IgA antibodies anti-TMEM191C-expressing cancer cells. Disclosed herein are conjugated dimeric IgA antibodies anti-ADAM20-expressing cancer cells.IgG Backbone

[0122] In an aspect, a disclosed IgG can comprise four polypeptide chains (i.e., two identical 50 kDa y heavy (H) chains and two identical 25 kDa K or light (L) chains - linked together by inter-chain disulfide bonds). In an aspect, a disclosed heavy chain can comprise an N-terminal variable domain (VH) and three constant domains (CHI, CH2, CH3) with an additional “hinge region” between CHI and CH2. In an aspect, a disclosed light chain can comprise an N-terminal variable domain (VL) and a constant domain (CL). In an aspect, a disclosed light chain can associate with the VH and CHI domains to form a Fab arm (“Fab” = fragment antigen binding).In an aspect, disclosed V regions can interact to form the in antigen-binding region - acquired through differential assembly of Variable, Diversity (VH only), and Joining gene segments and inclusion of somatic mutations. In an aspect, two heavy chain-light chain heterodimers (HL) can combine into a single antibody molecule (H2L2) via disulfide bonds in the hinge region and non- covalent interactions between the CH3 domains. In an aspect, the part of the antibody formed by the lower hinge region and the CH2 / CH3 domains is called “Fc” (“fragment crystalline”).TAS2R13

[0123] Disclosed herein is an antibody comprising an IgG backbone, wherein the antibody recognizes a TAS2R13-expressing cancer cell. Disclosed herein is an antibody targeting TAS2R13-expressing cancer cells comprising an IgG backbone.

[0124] In an aspect, a disclosed anti-TAS2R13 antibody can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the constant heavy chain region.

[0125] In an aspect, a disclosed IgG targeting TAS2R13-expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0126] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VH can comprise the sequence set forth in SEQ ID NO:20 or a fragment thereof. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:20. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:21 or a fragment thereof. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:21.

[0127] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VL can comprise the sequence set forth in SEQ ID NO:22 or a fragment thereof. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:22. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:23 or a fragment thereof. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:23.

[0128] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 02, SEQ ID NO: 03, and SEQ ID NO:04. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:06, and SEQ ID NO:07. In an aspect, a disclosed VH- CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:07, and SEQ ID NO:07.

[0129] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 08, SEQ ID NO: 09, and SEQ ID NO: 10. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13.

[0130] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising 13 amino acids can comprise 3 or more substitutions.

[0131] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed CDR comprising the sequence set forth in SEQ ID NO:09 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:02 and / or SEQ ID NO:03 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:08 and / or SEQ ID NO: 10 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:04 can further comprise 3 or more substitutions.

[0132] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ IDNO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04.

[0133] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10.

[0134] In an aspect, a disclosed antibody can target the extracellular domain of TAS2R13. In an aspect, a disclosed antibody can TAS2R13 expressed on the cell surface of a cancer cell. In an aspect, a disclosed antibody targeting TAS2R13 can be used in conjunction with an antibody targeting any other cancer antigen. In an aspect, a disclosed TAS2R13 antigen can comprise the sequence set forth in SEQ ID NO:OL In an aspect, a disclosed TAS2R13 antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:OLTable 1 - CDR Sequences of TAS2R13 #1

[0135] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VH can comprise the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:43. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43.

[0136] In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.

[0137] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32. In an aspect, a disclosed VH- CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32.

[0138] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35.

[0139] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising10 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH- CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0140] In an aspect of a disclosed anti-TAS2R13 antibody, a disclosed CDR comprising the sequence set forth in SEQ ID NO:28 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, and / or SEQ ID NO:29, and / or any combination thereof can further comprise 2 or more substitutions. In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29.

[0141] In an aspect of a disclosed anti-TAS2R13 antibody, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0142] In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a variation in the order of a disclosed VH, a disclosed linker, and a disclosed VL. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VH, a disclosed linker, and a disclosed VL in this order. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VL, a disclosed linker, and a disclosed VH in this order.

[0143] In an aspect, a disclosed VL can be located at the N-terminus of the VH. In an aspect, a disclosed extracellular domain comprising a TAS2R13 binding domain can comprise SEQ ID NO:42 and SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44.

[0144] In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.Table 2 - CDR Sequences of TAS2R13 #2

[0145] In an aspect, a disclosed antibody recognizing TAS2R13 binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a TAS2R13 binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carryinformation for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.

[0146] In an aspect, a disclosed signal peptide can be linked to a disclosed VH. In an aspect, a disclosed signal peptide can comprise the sequence set forth in any one SEQ ID NO:91 - SEQ ID NO: 107 and a disclosed VH comprising the sequence set forth in SEQ ID NO:20. In an aspect, a disclosed signal peptide can comprise the sequence set forth in SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 121, SEQ ID NO: 123, SEQ ID NO:89, or fragment thereof, and a disclosed VH can comprise the sequence set forth in SEQ ID NO:20.

[0147] In an aspect, a disclosed signal peptide can be encoded by the sequence set forth in SEQ ID NO: 118, SEQ ID NO: 120, SEQ ID NO: 122, SEQ ID NO: 124, or fragment thereof, and a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:21.TMEM191C

[0148] Disclosed herein is an antibody comprising an IgG backbone, wherein the antibody recognizes a TMEM191C-expressing cancer cell. Disclosed herein is an antibody targeting TMEM191C-expressing cancer cells comprising an IgG backbone.

[0149] In an aspect, a disclosed anti-TMEM191C antibody can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region. In an aspect, a disclosed IgG targeting TMEM191C- expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0150] TMEM191C can comprise the amino acid sequence set forth in SEQ ID NO:210. TMEM191C can comprise an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:210. TMEM191C can comprise the nucleotide sequence set forth in SEQ ID NO:211. TMEM191C can comprise a nucleotide sequence having at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:211.

[0151] In an aspect, a disclosed VH can comprise the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:84. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 84.

[0152] In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:86. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 86.

[0153] In an aspect, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74.

[0154] In an aspect, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 78, SEQ ID NO: 79, and SEQ ID NO: 80.

[0155] In an aspect, a disclosed VH-CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 10 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 11 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise1 or more substitutions. In an aspect, a disclosed VL-CDR comprising 8 amino acids can comprise2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0156] In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:76 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:75 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:70 and / or SEQ ID NO:77 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:69 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:71 can further comprise 3 or more substitutions.

[0157] In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.

[0158] In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.

[0159] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0160] In an aspect, a disclosed antibody can target the extracellular domain of TMEM191C. In an aspect, a disclosed antibody can TMEM191C expressed on the cell surface of a cancer cell. In an aspect, a disclosed antibody targeting TMEM191C can be used in conjunction with an antibody targeting any other cancer antigen. In an aspect, a disclosed TMEM191C antigen can comprise the sequence set forth in SEQ ID NO:68. In an aspect, a disclosed TMEM191C antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 68.

[0161] In an aspect, a disclosed antibody recognizing TMEM191C binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a TMEM191C binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.Table 3 - CDR Sequences of TMEM191CADAM20

[0162] Disclosed herein is an antibody comprising an IgG backbone, wherein the antibody recognizes a ADAM20-expressing cancer cell. Disclosed herein is an antibody targeting ADAM20-expressing cancer cells comprising an IgG backbone.

[0163] In an aspect, a disclosed anti-ADAM20 antibody can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0164] In an aspect, a disclosed IgG targeting ADAM20-expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0165] ADAM20 can comprise the amino acid sequence set forth in SEQ ID NO:205. ADAM20 can comprise an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:205. The extracellular domain of ADAM20 can comprise the amino acid sequence set forth in SEQ ID NO:206. The extracellular domain of ADAM20 can comprise an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:206. ADAM20 can comprise the nucleotide sequence set forth in SEQ ID NO:207. ADAM20 can comprise a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:207.

[0166] In an aspect, a disclosed VH can comprise the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:67. In an aspect, a disclosed VL can be encoded by a sequencehaving at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 67.

[0167] In an aspect, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54.

[0168] In an aspect, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57.

[0169] In an aspect, a disclosed VH-CDR comprising 8 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 14 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 10 amino acids can comprise 2 or more substitutions.

[0170] In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:74 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:46 or SEQ ID NO:47 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:49 or SEQ ID NO:51 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:48 can further comprise 3 or more substitutions.

[0171] In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48.In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48.

[0172] In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51.

[0173] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0174] In an aspect, a disclosed extracellular domain comprising a ADAM20 binding domain can comprise SEQ ID NO:64 and SEQ ID NO:66.

[0175] In an aspect, a disclosed antibody can target the extracellular domain of ADAM20. In an aspect, a disclosed antibody can ADAM20 expressed on the cell surface of a cancer cell. In an aspect, a disclosed antibody targeting ADAM20 can be used in conjunction with a disclosed antibody targeting any other cancer antigen. In an aspect, a disclosed ADAM20 antigen can comprise the sequence set forth in SEQ ID NO:206. In an aspect, a disclosed ADAM20 antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:206.

[0176] In an aspect, a disclosed antibody comprising a ADAM20 binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a ADAM20 binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the Nterminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.Table 4 - CDR Sequences of ADAM20

[0177] In an aspect, a disclosed conserved domain of a disclosed IgG antibody can comprise CHI, CH2, and CH3. In an aspect, a disclosed IgG antibody comprises two fragment antigen binding (Fab) regions that make up the arms of the classic Y shape and the Fc region that forms the stem. In an aspect, a disclosed IgG antibody can comprise two identical light chains and two identical heavy chains. In an aspect, a disclosed light chain and a disclosed heavy chain can be connected through a noncovalent interaction and can be crosslinked by a pair of conserved disulfide bonds.

[0178] In an aspect, a disclosed chain can comprise a conserved (CH1-3 and CL) sequence and a disclosed variable (VH and VL) sequence that fold into a similar structure (i.e., the immunoglobulin domain). In an aspect, a disclosed combination of variable and conserved sequences in a Fab can make up the antigen binding site with the variability of the V regions allowing the specificity of antigen binding.

[0179] In an aspect, a disclosed Fc receptor binding site and the carbohydrate attachment sites can be in the CH2 segment of the Fc region. As known to the art, the four classes of IgG subtypes differ in their CH2 sequences and carbohydrate attachment sites, thereby enabling different effector functions for each IgG subtype.

[0180] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20- targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed IgG antibody targeting TAS2R 13 -expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used in a method of treating a subject having pancreatic adenocarcinoma, mucinous ovarian cancer, appendiceal adenocarcinoma, ampullary carcinoma, small intestinal carcinoma, bladder adenocarcinoma, endometroid ovarian cancer, low grade serous ovarian cancer, endometrial carcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous lung cancer, colorectal adenocarcinoma, or pancreatic carcinoma.

[0181] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to (i) prevent and / or decrease the risk of developing metastases, (ii) prolong the survival of the subject, (iii) enhance and / or improve the subject's quality of life, (iv) reduce and / or minimize the likelihood of surgical intervention, (v) reduce and / or decrease the size of one or more tumors in the subject, (vi) eliminate one or more tumors in the subject, (vii) improve and / or restore normal metabolism of one or more organ systems in the subject, (viii) restore and / or improve one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation are, or (ix) any combination thereof.

[0182] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to prevent an undesired physiological change, disease, pathological condition, or disorder from occurring in the subject having cancer. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to inhibit a physiological change, disease, pathological condition, or disorder, z.e., arresting its development, in the subject. In an aspect, a disclosed IgG antibody targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cellscan be used to relieve a physiological change, disease, pathological condition, or disorder, i.e., causing regression of the disease, in the subject.

[0183] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to treat and / or prevent cancer, to prolong the survival of the subject, to prevent and / or decrease metastases, to protect the subject from metastasis, to reduce the risk of developing metastases, to increase the subject's survivability, to increase the length of time before metastasis, to reduce the likelihood of surgical intervention, to reduce the need for administration of one or more additional therapeutic agents or regimens, to reduce the size of one or more tumors in the subject, to reduce the size of one or more tumors in one or more organs in the subject, to eliminate one or more tumors in the subject, to reduce and / or eliminate the prevalence of one or more genomic aberrations, to restore normal metabolism of one or more organ systems in the subject, to restore one or more aspects of cellular homeostasis, cellular functionality, and / or metabolic dysregulation in a subject, to reduce and / or inhibit aberrant angiogenesis and / or vasculogenesis in one or more tissues and / or organs of the subject, or any combination thereof.

[0184] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve and / or can be used to enhance the quality of the subject's life when compared to a pre-treatment level. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve the subject's quality of life by at least 50% when compared to the subject's pre-treatment quality of life. In an aspect a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to diminish and / or decrease one or more symptoms associated with and / or related to the subject's cancer.

[0185] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used with one or more additional therapeutic agents. In an aspect, a disclosed therapeutic agent can comprise (i) one or more active agents, (ii) biologically active agents, (iii) one or more pharmaceutically active agents, (iv) one or more immune-based therapeutic agents, (v) one or more clinically approved agents, or (vi) a combination thereof. In an aspect, a disclosed anti-mutant KRAS antibody comprising an IgG backbone can be used with one or more targeted therapies.

[0186] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be included in a disclosed pharmaceutical formulation (discussed infra). In an aspect a disclosed IgG antibodytargeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20- targeting cancer cells can be administered to a subject having cancer in one or more routes of administration (discussed infra).

[0187] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be subjected to one or more validating and / or characterizing steps and / or protocols. For example, in an aspect, validating and / or characterizing one or more disclosed IgG antibodies targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can comprise measuring, ascertaining, and / or determining the purity and / or efficacy of the one or more disclosed IgG antibodies targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells and / or a pharmaceutical formulation thereof.

[0188] The following can be applied to any disclosed IgG antibody. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20- targeting cancer cells can be used in a method of treating a subject having pancreatic adenocarcinoma, mucinous ovarian cancer, appendiceal adenocarcinoma, ampullary carcinoma, small intestinal carcinoma, bladder adenocarcinoma, endometroid ovarian cancer, low grade serous ovarian cancer, endometrial carcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous lung cancer, colorectal adenocarcinoma, or pancreatic carcinoma.

[0189] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to (i) prevent and / or decrease the risk of developing metastases, (ii) prolong the survival of the subject, (iii) enhance and / or improve the subject's quality of life, (iv) reduce and / or minimize the likelihood of surgical intervention, (v) reduce and / or decrease the size of one or more tumors in the subject, (vi) eliminate one or more tumors in the subject, (vii) improve and / or restore normalmetabolism of one or more organ systems in the subject, (viii) restore and / or improve one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation are, or (ix) any combination thereof.

[0190] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to prevent an undesired physiological change, disease, pathological condition, or disorder from occurring in the subject having cancer. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to inhibit a physiological change, disease, pathological condition, or disorder, z.e., arresting its development, in the subject. In an aspect, a disclosed IgG antibody targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to relieve a physiological change, disease, pathological condition, or disorder, z.e., causing regression of the disease, in the subject.

[0191] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to treat and / or prevent cancer, to prolong the survival of the subject, to prevent and / or decrease metastases, to protect the subject from metastasis, to reduce the risk of developing metastases, to increase the subject's survivability, to increase the length of time before metastasis, to reduce the likelihood of surgical intervention, to reduce the need for administration of one or more additional therapeutic agents or regimens, to reduce the size of one or more tumors in the subject, to reduce the size of one or more tumors in one or more organs in the subject, to eliminate one or more tumors in the subject, to reduce and / or eliminate the prevalence of one or more genomic aberrations, to restore normal metabolism of one or more organ systems in the subject, to restore one or more aspects of cellular homeostasis, cellular functionality, and / or metabolic dysregulation in a subject, to reduce and / or inhibit aberrant angiogenesis and / or vasculogenesis in one or more tissues and / or organs of the subject, or any combination thereof.

[0192] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve and / or can be used to enhance the quality of the subject's life when compared to a pre-treatment level. In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve the subject's quality of life by at least 50% when compared to the subject's pre-treatment quality of life. In an aspect a disclosed IgG antibody targeting TAS2R13-expressing cancer cells,TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to diminish and / or decrease one or more symptoms associated with and / or related to the subject's cancer.

[0193] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used with one or more additional therapeutic agents. In an aspect, a disclosed therapeutic agent can comprise (i) one or more active agents, (ii) biologically active agents, (iii) one or more pharmaceutically active agents, (iv) one or more immune-based therapeutic agents, (v) one or more clinically approved agents, or (vi) a combination thereof. In an aspect, a disclosed anti-mutant KRAS antibody comprising an IgG backbone can be used with one or more targeted therapies.

[0194] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be included in a disclosed pharmaceutical formulation (discussed infra). In an aspect a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20- targeting cancer cells can be administered to a subject having cancer in one or more routes of administration (discussed infra).

[0195] In an aspect, a disclosed IgG antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be subjected to one or more validating and / or characterizing steps and / or protocols. For example, in an aspect, validating and / or characterizing one or more disclosed IgG antibodies targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can comprise measuring, ascertaining, and / or determining the purity and / or efficacy of the one or more disclosed IgG antibodies targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells and / or a pharmaceutical formulation thereof.

[0196] In an aspect, a disclosed IgG antibody can be used to stimulate cancer cell death through at least one of antibody-mediated cellular cytotoxicity (ADCC) and antibody-mediated cellular phagocytosis (ADCP). In an aspect, ADCC is an immune defense mechanism whereby a particular set of immune cells (effector cells) of the body actively engage and lyse a target cell. In an aspect, ADCC is an important cell-mediated innate immune response and functions as the body ’ s first-line of defense against pathogens and acts to limit and contain infections. In an aspect, ADCC is designed to kill the antibody-coated target cell through a non-phagocytic process. In an aspect, ADCC is characterized either by the targeted release of cytotoxic granules or by the expression of cell death-inducing molecules. In an aspect, ADCC is typically initiated when specific antibodies of the host recognize and bind the membrane-surface antigens of the targetcells and simultaneously engage the Fc receptors (FcR) on the effector cell surface. In an aspect, most common effector cells that mediate ADCC are the natural killer (NK) cells, although monocytes, macrophages, neutrophils, eosinophils and dendritic cells are also capable of mediating an ADCC response. In an aspect, ADCC is a rather fast response, the efficacy varies depending on the several parameters such as the antigen density on the surface of the target cells and the affinity of the antigen-antibody interaction as well as characteristics of Fc fragments that determines antibody interactions with varies members of Fc receptor family. In an aspect, a disclosed IgG antibody can be incorporated into ADCC-mediated cancer killing antibodies.IgA Backbone

[0197] In an aspect, a disclosed IgA monomer can comprise two identical Fab regions that bind antigen (e.g., TAS2R13, TMEM191C, or ADAM20) linked through the hinge region to the Fc region, which mediates effector mechanisms. In an aspect, both heavy and light chains are folded into globular domains, four in each heavy chain (from the N-terminus VH, Cal, Ca2, and Ca3) and two in each light chain (VL and CL). In an aspect, each domain can adopt the characteristic “immunoglobulin fold”, comprising a 110 residue P-sheet sandwich of anti-parallel strands arranged around a stabilizing internal disulfide bond.

[0198] In an aspect, there can be close pairing of domains between neighboring chains (VH with VL, Cal with CL, and Ca3 with Ca3). In an aspect, inter-chain disulfide bridges can further stabilize the structure. In an aspect, these can be found between heavy chains in the Ca2 domain of IgAl and IgA2. In an aspect, disulfide bridges can occur between the heavy and light chains in IgA. In an aspect, in dimeric IgA (dlgA), the Fc regions of the two monomers can be linked end to end through disulfide bridges to the J chain. In an aspect, the penultimate residue of the tailpiece, Cys471, of one of the heavy chains of each monomer forms a disulfide bridge to the J chain. In an aspect, both Fc domains also contribute to efficient dimer formation.TAS2R13

[0199] Disclosed herein is an antibody comprising a dimeric IgA backbone, wherein the antibody recognizes a TAS2R13-expressing cancer cell. Disclosed herein is an antibody targeting TAS2R13-expressing cancer cells comprising a dimeric IgA backbone. Disclosed herein is an antibody, comprising a dimeric IgA backbone comprising two monomers, wherein each of the monomers comprises a variable light chains region (VL) comprising 3 CDRs and a variable heavy chain region (VH) comprising 3 CDRs; wherein the VH is linked to a conserved heavy chain region; wherein the two monomers are linked together; and wherein the antibody recognizes TAS2R13-expressing cancer cells. Disclosed herein is antibody recognizing TAS2R13- expressing cancer cells comprising a dimeric IgA backbone comprising two monomers, whereineach of the monomers comprises a variable light chains region (VL) comprising 3 CDRs, and a variable heavy chain region (VH) comprising 3 CDRs; wherein the VH is linked to a conserved heavy chain region; wherein the two monomers are linked together.

[0200] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed anti-TAS2R13 antibody can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the constant heavy chain region.

[0201] In an aspect, a disclosed dimeric IgA targeting TAS2R13-expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0202] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VH can comprise the sequence set forth in SEQ ID NO:20 or a fragment thereof. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:20. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:21 or a fragment thereof. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:21.

[0203] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VL can comprise the sequence set forth in SEQ ID NO:22 or a fragment thereof. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:22. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:23 or a fragment thereof. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:23.

[0204] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH-CDR can be encoded by the sequenceset forth in any one of SEQ ID NO:05, SEQ ID NO:06, and SEQ ID NO:07. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:07, and SEQ ID NO:07.

[0205] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13.

[0206] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising 13 amino acids can comprise 3 or more substitutions.

[0207] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed CDR comprising the sequence set forth in SEQ ID NO:09 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:02 and / or SEQ ID NO:03 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:08 and / or SEQ ID NO: 10 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:04 can further comprise 3 or more substitutions.

[0208] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VHcan comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04.

[0209] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10.

[0210] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VH can comprise the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:43. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43.

[0211] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VL can comprise the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.

[0212] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least80% identity to the sequence set forth in any one of SEQ ID NO: 30, SEQ ID NO: 31, and SEQ ID NO:32.

[0213] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO 35.

[0214] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH- CDR comprising 10 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0215] In an aspect of an antibody comprising a dimeric IgA backbone, a disclosed CDR comprising the sequence set forth in SEQ ID NO:28 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, and / or SEQ ID NO:29, and / or any combination thereof can further comprise 2 or more substitutions. In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one ofSEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29.

[0216] In an aspect of an antibody comprising a dimeric IgA backbone, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0217] In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a variation in the order of a disclosed VH, a disclosed linker, and a disclosed VL. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VH, a disclosed linker, and a disclosed VL in this order. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VL, a disclosed linker, and a disclosed VH in this order.

[0218] In an aspect, a disclosed VL can be located at the N-terminus of the VH. In an aspect, a disclosed extracellular domain comprising a TAS2R13 binding domain can comprise SEQ ID NO:42 and SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44.

[0219] In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.

[0220] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0221] In an aspect, a disclosed dimeric IgA antibody can target the extracellular domain of TAS2R13. In an aspect, a disclosed dimeric IgA antibody can TAS2R13 expressed on the cell surface of a cancer cell. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13 can be used in conjunction with an antibody targeting any other cancer antigen. In an aspect, a disclosed TAS2R13 antigen can comprise the sequence set forth in SEQ ID NO:01. In an aspect, a disclosed TAS2R13 antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01.

[0222] In an aspect of an antibody comprising a dimeric IgA backbone, a first disclosed monomer can be connected to a second disclosed monomer via a J chain. In an aspect, a disclosed J chain can comprise the sequence set forth in SEQ ID NO:233 or a fragment thereof. In an aspect, a disclosed J chain can comprise the sequence set forth in SEQ ID NO:233 or a fragment thereof. The human JCHAIN gene (NCBI gene ID:3512) is located on the ql 3.3 region of chromosome 4. With a total of 4 exons, the human JCHAIN gene spans about 9.8 kb. In an aspect, J chain can mediate the polymerization of IgA.

[0223] In an aspect, a disclosed antibody recognizing TAS2R13 binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a TAS2R13 binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent VL can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent VL crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.TMEM191C

[0224] Disclosed herein is an antibody comprising a dimeric IgA backbone, wherein the antibody recognizes a TMEM191C-expressing cancer cell. Disclosed herein is a dimeric IgA antibody targeting TMEM191C-expressing cancer cells comprising an IgG backbone. Disclosed herein isan antibody, comprising a dimeric IgA backbone comprising two monomers, wherein each of the monomers comprises a variable light chains region (VL) comprising 3 CDRs and a variable heavy chain region (VH) comprising 3 CDRs; wherein the VH is linked to a conserved heavy chain region; wherein the two monomers are linked together; and wherein the antibody recognizes TMEM191C-expressing cancer cells.

[0225] In an aspect, a disclosed anti-TMEM191C dimeric IgA antibody can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0226] In an aspect, a disclosed dimeric IgA antibody targeting TMEM191C-expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0227] TMEM191C can comprise the amino acid sequence set forth in SEQ ID NO:210. TMEM191C can comprise an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:210. TMEM191C can comprise the nucleotide sequence set forth in SEQ ID NO:211. TMEM191C can comprise a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:211.

[0228] In an aspect, a disclosed VH can comprise the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:84. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 84.

[0229] In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:86. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 86.

[0230] In an aspect, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74.

[0231] In an aspect, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 78, SEQ ID NO: 79, and SEQ ID NO: 80.

[0232] In an aspect, a disclosed VH-CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 10 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 11 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise1 or more substitutions. In an aspect, a disclosed VL-CDR comprising 8 amino acids can comprise2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0233] In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:76 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:75 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:70 and / or SEQ ID NO:77 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:69 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:71SEQ ID NO:71 can further comprise 3 or more substitutions.

[0234] In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71.

[0235] In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.

[0236] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0237] In an aspect, a disclosed antibody can target the extracellular domain of TMEM191C. In an aspect, a disclosed antibody can TMEM191C expressed on the cell surface of a cancer cell. In an aspect, a disclosed antibody targeting TMEM191C can be used in conjunction with an antibody targeting any other cancer antigen. In an aspect, a disclosed TMEM191C antigen can comprise the sequence set forth in SEQ ID NO:68. In an aspect, a disclosed TMEM191C antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 68.

[0238] In an aspect, a disclosed antibody recognizing TMEM191C binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a TMEM191C binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the Nterminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.ADAM20

[0239] Disclosed herein is an antibody comprising a dimeric IgA backbone, wherein the antibody recognizes an ADAM20-expressing cancer cell. Disclosed herein is an antibody targeting ADAM20-expressing cancer cells comprising a dimeric IgA backbone. Disclosed herein is an antibody, comprising a dimeric IgA backbone comprising two monomers, wherein each of the monomers comprises a variable light chains region (VL) comprising 3 CDRs and a variable heavy chain region (VH) comprising 3 CDRs; wherein the VH is linked to a conserved heavy chain region; wherein the two monomers are linked together; and wherein the antibody recognizes ADAM20-expressing cancer cells.

[0240] In an aspect, a disclosed anti-ADAM20 dimeric IgA antibody can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0241] In an aspect, a disclosed dimeric IgA targeting ADAM20-expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0242] ADAM20 can comprise the amino acid sequence set forth in SEQ ID NO:205. ADAM20 can comprise an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:205. The extracellular domain of ADAM20 can comprise the amino acid sequence set forth in SEQ ID NO:206. The extracellular domain of ADAM20 can comprise an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:206. ADAM20 can comprise the nucleotide sequence set forth in SEQ ID NO:207. ADAM20 can comprise a nucleotide sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:207.

[0243] In an aspect, a disclosed VH can comprise the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:67. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 67.

[0244] In an aspect, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54.

[0245] In an aspect, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57.

[0246] In an aspect, a disclosed VH-CDR comprising 8 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 14 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 10 amino acids can comprise 2 or more substitutions.

[0247] In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:74 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:46 or SEQ ID NO:47 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:49 or SEQ ID NO:51 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:48 can further comprise 3 or more substitutions.

[0248] In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48.

[0249] In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51.

[0250] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0251] In an aspect, a disclosed extracellular domain comprising a ADAM20 binding domain can comprise SEQ ID NO:64 and SEQ ID NO:66.

[0252] In an aspect, a disclosed dimeric IgA antibody can target the extracellular domain of ADAM20. In an aspect, a disclosed dimeric IgA antibody can ADAM20 expressed on the cellsurface of a cancer cell. In an aspect, a disclosed dimeric IgA antibody targeting ADAM20 can be used in conjunction with a disclosed antibody targeting any other cancer antigen. In an aspect, a disclosed ADAM20 antigen can comprise the sequence set forth in SEQ ID NO:206. In an aspect, a disclosed ADAM20 antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:206.

[0253] In an aspect, a disclosed antibody comprising a ADAM20 binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a ADAM20 binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.

[0254] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a method of treating a subject having pancreatic adenocarcinoma, mucinous ovarian cancer, appendiceal adenocarcinoma, ampullary carcinoma, small intestinal carcinoma, bladder adenocarcinoma, endometroid ovarian cancer, low grade serous ovarian cancer, endometrial carcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous lung cancer, colorectal adenocarcinoma, or pancreatic carcinoma.

[0255] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to (i) prevent and / or decrease the risk of developing metastases, (ii) prolong the survival of the subject, (iii) enhance and / or improve the subject's quality of life, (iv) reduce and / or minimize the likelihood of surgical intervention, (v) reduce and / or decrease the size of one or more tumors in the subject, (vi) eliminate one or more tumors in the subject, (vii) improve and / or restore normal metabolism of one or more organ systems in the subject, (viii) restore and / or improve one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation are, or (ix) any combination thereof.

[0256] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to prevent an undesired physiological change, disease, pathological condition, or disorder from occurring in the subject having cancer. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to inhibit a physiological change, disease, pathological condition, or disorder, z.e., arresting its development, in the subject. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to relieve a physiological change, disease, pathological condition, or disorder, z.e., causing regression of the disease, in the subject.

[0257] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to treat and / or prevent cancer, to prolong the survival of the subject, to prevent and / or decrease metastases, to protect the subject from metastasis, to reduce the risk of developing metastases, to increase the subject's survivability, to increase the length of time before metastasis, to reduce the likelihood of surgical intervention, to reduce the need for administration of one or more additional therapeutic agents or regimens, to reduce the size of one or more tumors in the subject, to reduce the size of one or more tumors in one or more organs in the subject, to eliminate one or more tumors in the subject, to reduce and / or eliminate the prevalence of one or more genomic aberrations, to restore normal metabolism of one or more organ systems in the subject, to restore one or more aspects of cellular homeostasis, cellular functionality, and / or metabolic dysregulation in a subject, to reduce and / or inhibit aberrant angiogenesis and / or vasculogenesis in one or more tissues and / or organs of the subject, or any combination thereof.

[0258] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improveand / or can be used to enhance the quality of the subject's life when compared to a pre-treatment level. In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve the subject's quality of life by at least 50% when compared to the subject's pre-treatment quality of life. In an aspect a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to diminish and / or decrease one or more symptoms associated with and / or related to the subject's cancer.

[0259] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used with one or more additional therapeutic agents. In an aspect, a disclosed therapeutic agent can comprise (i) one or more active agents, (ii) biologically active agents, (iii) one or more pharmaceutically active agents, (iv) one or more immune-based therapeutic agents, (v) one or more clinically approved agents, or (vi) a combination thereof. In an aspect, a disclosed anti-mutant KRAS antibody comprising an dimeric IgA backbone can be used with one or more targeted therapies.

[0260] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be included in a disclosed pharmaceutical formulation (discussed infra). In an aspect a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be administered to a subject having cancer in one or more routes of administration (discussed infra).

[0261] In an aspect, a disclosed dimeric IgA antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be subjected to one or more validating and / or characterizing steps and / or protocols. For example, in an aspect, validating and / or characterizing one or more disclosed dimeric IgA antibodies targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can comprise measuring, ascertaining, and / or determining the purity and / or efficacy of the one or more disclosed dimeric IgA antibodies targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells and / or a pharmaceutical formulation thereof.

[0262] In an aspect, a disclosed IgA can play a critical role in mucosal immunity. In an aspect, a disclosed dimeric IgA molecule is relatively smaller in size than a disclosed IgM molecule. In an aspect, a disclosed dimeric IgA can be manufactured by expression in vitro to include two IgA monomers and a J-chain. In an aspect, a disclosed IgA can comprise three heavy chain constantdomains (i.e., CHI, CH2, and CH3). In an aspect, a disclosed IgA can comprise a C-terminal tail or tailpiece. In an aspect, IgA can have two subtypes (i.e., IgAl and IgA2).

[0263] In an aspect, a disclosed constant domain (CH) of a disclosed IgAl antibody can comprise the amino acid sequence set forth in SEQ ID NO:226 or a fragment thereof. In an aspect, a disclosed CHI region of IgAl can comprise from about amino acid 6 to about amino acid 98 of SEQ ID NO:226. In an aspect, a disclosed CH2 region of IgAl can comprise from about amino acid 125 to about amino acid 220 of SEQ ID NO:226. In an aspect, a disclosed CH3 region of IgAl can comprise from about amino acid 228 to about amino acid 330 of SEQ ID NO:226. In an aspect, a disclosed tailpiece of IgAl can comprise from about amino acid 331 to about amino acid 352 of SEQ ID NO:226.

[0264] In an aspect, a disclosed constant domain (CH) of a disclosed IgA2 antibody can comprise the amino acid sequence set forth in SEQ ID NO:227 or a fragment thereof. In an aspect, a disclosed CHI region of IgA2 can comprise from about amino acid 6 to about amino acid 98 of SEQ ID NO:227. In an aspect, a disclosed CH2 region of IgA2 can comprise from about amino acid 112 to about amino acid 207 of SEQ ID NO:227. In an aspect, a disclosed CH3 region of IgA2 can comprise from about amino acid 215 to about amino acid 317 of SEQ ID NO:227. In an aspect, a disclosed tailpiece of IgA2 can comprise from about amino acid 318 to about amino acid 340 of SEQ ID NO:227. In an aspect, a disclosed dimeric IgA can comprise a secretory component (i.e., SEQ ID NO:228).

[0265] In an aspect, a disclosed IgA antibody or disclosed dimeric IgA antibody can be used to stimulate cancer cell death through at least one of antibody-mediated cellular cytotoxicity (ADCC) and antibody-mediated cellular phagocytosis (ADCP). In an aspect, ADCC is an immune defense mechanism whereby a particular set of immune cells (effector cells) of the body actively engage and lyse a target cell. In an aspect, ADCC is an important cell-mediated innate immune response and functions as the body’s first-line of defense against pathogens and acts to limit and contain infections. In an aspect, ADCC is designed to kill the antibody-coated target cell through a non- phagocytic process. In an aspect, ADCC is characterized either by the targeted release of cytotoxic granules or by the expression of cell death-inducing molecules. In an aspect, ADCC is typically initiated when specific antibodies of the host recognize and bind the membrane-surface antigens of the target cells and simultaneously engage the Fc receptors (FcR) on the effector cell surface. In an aspect, most common effector cells that mediate ADCC are the natural killer (NK) cells, although monocytes, macrophages, neutrophils, eosinophils and dendritic cells are also capable of mediating an ADCC response. In an aspect, ADCC is a rather fast response, the efficacy varies depending on the several parameters such as the antigen density on the surface of the target cellsand the affinity of the antigen-antibody interaction as well as characteristics of Fc fragments that determine antibody interactions with varies members of Fc receptor family. In an aspect, a disclosed IgG antibody can be incorporated into ADCC-mediated cancer killing antibodies.2. Single Chain Variable Fragment (scFv)

[0266] Disclosed herein are single chain variable fragment (scFv) comprising antigen binding domains targeting antigens expressed on cancer cells. Disclosed herein are scFv comprising a TAS2R13-antigen binding domain. Disclosed herein are scFv comprising a TMEM191C-antigen binding domain. Disclosed herein are scFv comprising a ADAM20-antigen binding domain.TAS2R13

[0267] In an aspect, a disclosed anti-TAS2R13 scFv can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs.

[0268] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VH can comprise the sequence set forth in SEQ ID NO:20 or a fragment thereof. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:20. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:21 or a fragment thereof. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:21.

[0269] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VL can comprise the sequence set forth in SEQ ID NO:22 or a fragment thereof. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:22. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:23 or a fragment thereof. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:23.

[0270] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 02, SEQ ID NO: 03, and SEQ ID NO:04. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth inany one of SEQ ID NO:05, SEQ ID NO:06, and SEQ ID NO:07. In an aspect, a disclosed VH- CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:07, and SEQ ID NO:07.

[0271] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 08, SEQ ID NO: 09, and SEQ ID NO: 10. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13.

[0272] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising 13 amino acids can comprise 3 or more substitutions.

[0273] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed CDR comprising the sequence set forth in SEQ ID NO:09 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:02 and / or SEQ ID NO:03 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:08 and / or SEQ ID NO: 10 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:04 can further comprise 3 or more substitutions.

[0274] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO: 02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04.

[0275] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO: 08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10.

[0276] In an aspect, a disclosed anti-TAS2R13 scFv can target the extracellular domain of TAS2R13. In an aspect, a disclosed anti-TAS2R13 scFv can target TAS2R13 expressed on the cell surface of a cancer cell. In an aspect, a disclosed anti-TAS2R13 scFv targeting TAS2R13 can be used in conjunction with an antibody targeting any other cancer antigen. In an aspect, a disclosed TAS2R13 antigen can comprise the sequence set forth in SEQ ID NO:OL In an aspect, a disclosed TAS2R13 antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:OL Table 1, for example, provides CDR sequences for a first exemplary scFv targeting TAS2R13.

[0277] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VH can comprise the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:43. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43.

[0278] In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.

[0279] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprisethe sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32. In an aspect, a disclosed VH- CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32.

[0280] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35.

[0281] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 10 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL- CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0282] In an aspect of a disclosed anti-TAS2R13 scFv, a disclosed CDR comprising the sequence set forth in SEQ ID NO:28 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, and / or SEQ ID NO:29, and / or any combination thereof can further comprise 2 or more substitutions. In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25,and SEQ ID NO:26. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29.

[0283] In an aspect of a disclosed anti-TAS2R13 scFv, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0284] In an aspect, a disclosed anti-TAS2R13 scFv comprising a TAS2R13 binding domain can comprise a variation in the order of a disclosed VH, a disclosed linker, and a disclosed VL. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VH, a disclosed linker, and a disclosed VL in this order. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VL, a disclosed linker, and a disclosed VH in this order.

[0285] In an aspect, a disclosed VL can be located at the N-terminus of the VH. In an aspect, a disclosed extracellular domain comprising a TAS2R13 binding domain can comprise SEQ ID NO:42 and SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44.

[0286] In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence setforth in SEQ ID NO:43, a disclosed linker, and a VL encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45. Table 2, for example, provides CDR sequences for a second exemplary scFv targeting TAS2R13.

[0287] In an aspect a disclosed anti-TAS2R13 scFv recognizing TAS2R13 binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect a disclosed anti-TAS2R13 scFv comprising a TAS2R13 binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.TMEM191C

[0288] In an aspect, a disclosed anti-TMEM191C scFv can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs.

[0289] In an aspect of a disclosed anti-TMEM191C scFv, a disclosed VH can comprise the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:84. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:84.

[0290] In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:86. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 86.

[0291] In an aspect, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71 SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74.

[0292] In an aspect, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80.

[0293] In an aspect, a disclosed VH-CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 10 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 11 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise1 or more substitutions. In an aspect, a disclosed VL-CDR comprising 8 amino acids can comprise2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0294] In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:76 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:75 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:70 and / or SEQ ID NO:77 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:69 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:71SEQ ID NO:71 can further comprise 3 or more substitutions.

[0295] In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71 SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO: 77.

[0296] In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO: 75 SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.

[0297] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0298] In an aspect, a disclosed antibody can target the extracellular domain of TMEM191C. In an aspect, a disclosed anti-TMEM191C scFv expressed on the cell surface of a cancer cell. In an aspect, a disclosed anti-TMEM191C scFv can be used in conjunction with an antibody targeting any other cancer antigen. In an aspect, a disclosed TMEM191C antigen can comprise the sequence set forth in SEQ ID NO:68. In an aspect, a disclosed TMEM191C antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:68.

[0299] In an aspect, a disclosed anti-TMEM191C scFv binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a disclosed anti-TMEM191C scFv can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry informationfor protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra.ADAM20

[0300] In an aspect, a disclosed anti-ADAM20 scFv can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs.

[0301] In an aspect of a disclosed anti-ADAM20 scFv, a disclosed VH can comprise the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VL can comprise the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:67. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:67.

[0302] In an aspect, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54.

[0303] In an aspect, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57.

[0304] In an aspect, a disclosed anti-ADAM20 scFv, a disclosed VH-CDR comprising 8 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 14 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VL-CDR comprising9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising10 amino acids can comprise 2 or more substitutions.

[0305] In an aspect, a disclosed anti-ADAM20 scFv, a disclosed CDR comprising the sequence set forth in SEQ ID NO:74 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:46 or SEQ ID NO:47 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:49 or SEQ ID NO:51 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:48 can further comprise 3 or more substitutions.

[0306] In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48.

[0307] In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51.

[0308] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0309] In an aspect, a disclosed extracellular domain comprising a ADAM20 binding domain can comprise SEQ ID NO:64 and SEQ ID NO:66.

[0310] In an aspect, a disclosed anti-ADAM20 scFv can target the extracellular domain of ADAM20. In an aspect, a disclosed antibody can ADAM20 expressed on the cell surface of a cancer cell. In an aspect, a disclosed scFv targeting ADAM20 can be used in conjunction with a disclosed antibody targeting any other cancer antigen. In an aspect, a disclosed ADAM20 antigen can comprise the sequence set forth in SEQ ID NO:206. In an aspect, a disclosed ADAM20 antigen can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:206.

[0311] In an aspect, a disclosed scFv comprising a ADAM20 binding domain can further comprise a signal peptide. Signal peptides are known to the art. In an aspect, a disclosed antibody comprising a ADAM20 binding domain can start with a disclosed signal peptide (SP). In an aspect, a disclosed signal peptide can be located at the N terminus of a protein and can carry information for protein post-translational assembly in the endoplasmic reticulum (ER) and Golgi organelle and expression on the membrane. In an aspect, a disclosed SP can be located at the N terminus of a nascent antibody can be identified by the signal recognition particle (SRP) while the protein is still translating in the ribosome. In an aspect, after a disclosed nascent antibody crosses the ER membrane, the signal peptide is cleaved off by a signal peptide peptidase (SPP). In an aspect, a disclosed signal peptide can comprise any known signal peptide or any known signal peptide known to function in mammalian cells. For example, in an aspect, a disclosed signal peptide can be a signal peptide described supra. Table 4, for example, provides CDR sequences for an exemplary scFv targeting ADAM20.

[0312] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressingcancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a method of treating a subject having pancreatic adenocarcinoma, mucinous ovarian cancer, appendiceal adenocarcinoma, ampullary carcinoma, small intestinal carcinoma, bladder adenocarcinoma, endometroid ovarian cancer, low grade serous ovarian cancer, endometrial carcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous lung cancer, colorectal adenocarcinoma, or pancreatic carcinoma.

[0313] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to (i) prevent and / or decrease the risk of developing metastases, (ii) prolong the survival of the subject, (iii) enhance and / or improve the subject's quality of life, (iv) reduce and / or minimize the likelihood of surgical intervention, (v) reduce and / or decrease the size of one or more tumors in the subject, (vi) eliminate one or more tumors in the subject, (vii) improve and / or restore normal metabolism of one or more organ systems in the subject, (viii) restore and / or improve one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation are, or (ix) any combination thereof.

[0314] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to prevent an undesired physiological change, disease, pathological condition, or disorder from occurring in the subject having cancer. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to inhibit a physiological change, disease, pathological condition, or disorder, z.e., arresting its development, in the subject. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to relieve a physiological change, disease, pathological condition, or disorder, z.e., causing regression of the disease, in the subject.

[0315] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to treat and / or prevent cancer, to prolong the survival of the subject, to prevent and / or decrease metastases, to protect thesubject from metastasis, to reduce the risk of developing metastases, to increase the subject's survivability, to increase the length of time before metastasis, to reduce the likelihood of surgical intervention, to reduce the need for administration of one or more additional therapeutic agents or regimens, to reduce the size of one or more tumors in the subject, to reduce the size of one or more tumors in one or more organs in the subject, to eliminate one or more tumors in the subject, to reduce and / or eliminate the prevalence of one or more genomic aberrations, to restore normal metabolism of one or more organ systems in the subject, to restore one or more aspects of cellular homeostasis, cellular functionality, and / or metabolic dysregulation in a subject, to reduce and / or inhibit aberrant angiogenesis and / or vasculogenesis in one or more tissues and / or organs of the subject, or any combination thereof.

[0316] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve and / or can be used to enhance the quality of the subject's life when compared to a pre-treatment level. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve the subject's quality of life by at least 50% when compared to the subject's pre-treatment quality of life. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to diminish and / or decrease one or more symptoms associated with and / or related to the subject's cancer.

[0317] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used with one or more additional therapeutic agents. In an aspect, a disclosed therapeutic agent can comprise (i) one or more active agents, (ii) biologically active agents, (iii) one or more pharmaceutically active agents, (iv) one or more immune-based therapeutic agents, (v) one or more clinically approved agents, or (vi) a combination thereof. In an aspect, a disclosed anti-mutant KRAS antibody comprising an IgG backbone can be used with one or more targeted therapies.

[0318] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be included in a disclosed pharmaceutical formulation (discussed infra). In an aspect, a disclosed scFv targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be administered to a subject having cancer in one or more routes of administration (discussed infra).

[0319] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be subjected to one or morevalidating and / or characterizing steps and / or protocols. For example, in an aspect, validating and / or characterizing one or more disclosed scFvs targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can comprise measuring, ascertaining, and / or determining the purity and / or efficacy of the one or more disclosed scFvs targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells and / or a pharmaceutical formulation thereof.

[0320] The following can be applied to any disclosed scFv. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20- targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method. In an aspect, a disclosed scFv targeting TAS2R13- expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used in a disclosed method of treating a subject having cancer. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used in a method of treating a subject having pancreatic adenocarcinoma, mucinous ovarian cancer, appendiceal adenocarcinoma, ampullary carcinoma, small intestinal carcinoma, bladder adenocarcinoma, endometroid ovarian cancer, low grade serous ovarian cancer, endometrial carcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous lung cancer, colorectal adenocarcinoma, or pancreatic carcinoma.

[0321] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to (i) prevent and / or decrease the risk of developing metastases, (ii) prolong the survival of the subject, (iii) enhance and / or improve the subject's quality of life, (iv) reduce and / or minimize the likelihood of surgical intervention, (v) reduce and / or decrease the size of one or more tumors in the subject, (vi) eliminate one or more tumors in the subject, (vii) improve and / or restore normal metabolism of one or more organ systems in the subject, (viii) restore and / or improve one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation are, or (ix) any combination thereof.

[0322] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to prevent an undesired physiological change, disease, pathological condition, or disorder from occurring in the subjecthaving cancer. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to inhibit a physiological change, disease, pathological condition, or disorder, z.e., arresting its development, in the subject. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to relieve a physiological change, disease, pathological condition, or disorder, z.e., causing regression of the disease, in the subject.

[0323] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to treat and / or prevent cancer, to prolong the survival of the subject, to prevent and / or decrease metastases, to protect the subject from metastasis, to reduce the risk of developing metastases, to increase the subject's survivability, to increase the length of time before metastasis, to reduce the likelihood of surgical intervention, to reduce the need for administration of one or more additional therapeutic agents or regimens, to reduce the size of one or more tumors in the subject, to reduce the size of one or more tumors in one or more organs in the subject, to eliminate one or more tumors in the subject, to reduce and / or eliminate the prevalence of one or more genomic aberrations, to restore normal metabolism of one or more organ systems in the subject, to restore one or more aspects of cellular homeostasis, cellular functionality, and / or metabolic dysregulation in a subject, to reduce and / or inhibit aberrant angiogenesis and / or vasculogenesis in one or more tissues and / or organs of the subject, or any combination thereof.

[0324] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve and / or can be used to enhance the quality of the subject's life when compared to a pre-treatment level. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to improve the subject's quality of life by at least 50% when compared to the subject's pre-treatment quality of life. In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be used to diminish and / or decrease one or more symptoms associated with and / or related to the subject's cancer.

[0325] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be used with one or more additional therapeutic agents. In an aspect, a disclosed therapeutic agent can comprise (i) one or more active agents, (ii) biologically active agents, (iii) one or more pharmaceutically active agents, (iv) one or more immune-based therapeutic agents, (v) one or more clinically approved agents, or(vi) a combination thereof. In an aspect, a disclosed anti-mutant KRAS antibody comprising an IgG backbone can be used with one or more targeted therapies.

[0326] In an aspect, a disclosed scFv antibody targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be included in a disclosed pharmaceutical formulation (discussed infra). In an aspect a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can be administered to a subject having cancer in one or more routes of administration (discussed infra).

[0327] In an aspect, a disclosed scFv targeting TAS2R13-expressing cancer cells, TMEM191C- expressing cancer cells, or ADAM20-targeting cancer cells can be subjected to one or more validating and / or characterizing steps and / or protocols. For example, in an aspect, validating and / or characterizing one or more disclosed scFvs targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells can comprise measuring, ascertaining, and / or determining the purity and / or efficacy of the one or more disclosed scFvs targeting TAS2R13-expressing cancer cells, TMEM191C-expressing cancer cells, or ADAM20-targeting cancer cells and / or a pharmaceutical formulation thereof.

[0328] In an aspect, a disclosed scFv can be used to stimulate cancer cell death through at least one of antibody-mediated cellular cytotoxicity (ADCC) and antibody-mediated cellular phagocytosis (ADCP). In an aspect, ADCC is an immune defense mechanism whereby a particular set of immune cells (effector cells) of the body actively engage and lyse a target cell. In an aspect, ADCC is an important cell-mediated innate immune response and functions as the body ’ s first-line of defense against pathogens and acts to limit and contain infections. In an aspect, ADCC is designed to kill the antibody-coated target cell through a non-phagocytic process. In an aspect, ADCC is characterized either by the targeted release of cytotoxic granules or by the expression of cell death-inducing molecules. In an aspect, ADCC is typically initiated when specific antibodies of the host recognize and bind the membrane-surface antigens of the target cells and simultaneously engage the Fc receptors (FcR) on the effector cell surface. In an aspect, most common effector cells that mediate ADCC are the natural killer (NK) cells, although monocytes, macrophages, neutrophils, eosinophils and dendritic cells are also capable of mediating an ADCC response. In an aspect, ADCC is a rather fast response, the efficacy varies depending on the several parameters such as the antigen density on the surface of the target cells and the affinity of the antigen-antibody interaction as well as characteristics of Fc fragments that determines antibody interactions with varies members of Fc receptor family. In an aspect, adisclosed scFv can be incorporated into ADCC-mediated cancer killing antibodies. In an aspect, a disclosed scFv can be incorporated into a disclosed BiTE (discussed infra).3. Antibody Drug Conjugates

[0329] Disclosed herein is an antibody drug conjugate comprising a disclosed antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed anti-TAS2R13 antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed anti-TMEM191C antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed anti-ADAM20 antibody conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity.

[0330] Disclosed herein is an antibody drug conjugate comprising a disclosed IgG antibody recognizing TAS2R13-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed IgG antibody recognizing TMEM191C-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed IgG antibody recognizing ADAM20-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity.

[0331] Disclosed herein is an antibody drug conjugate comprising a disclosed dimeric IgA antibody recognizing TAS2R 13 -expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed dimeric IgA antibody recognizing TMEM191C-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity. Disclosed herein is an antibody drug conjugate comprising a disclosed dimeric IgA antibody targeting ADAM20-expressing cancer cells conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity.

[0332] In an aspect, a disclosed ADC can allow selective delivery of potent chemotherapeutic agents to targeted cancer cells (e.g., cancer cells expressing TAS2R13, TMEM191C, or ADAM20), resulting in improved efficacy, reduced systemic toxicity, and improved pharmacokinetics, pharmacodynamics, and biodistribution compared to conventional chemotherapy. In an aspect, a disclosed cytotoxic agent in a disclosed ADC can comprise (i) enediynes such as calicheamicin and uncialamycin; (ii) tubulysins; (iii) CC-1065 and duocarmycin; (iv) epothilones; (v) auristatins; (vi) pyrrolobezodiazepine (PBD) dimers; (vii) maytansinoids (e.g., DM1 and DM4); and (viii) tubulin inhibitors (e.g., polymerization inhibitorsinclude halichondrins (such as eribulin), vinca alkaloids (such as vincristine, vinblastine, vinorelbine, and vindesine), dolastatins (such as MMAE and MMAF)). In an aspect, a disclosed ADC can comprise a disclosed antibody and any known chemotherapeutic agent.

[0333] In an aspect of a disclosed ADC, a disclosed antibody can be conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity via a chemical linker. In an aspect, a disclosed linker can be a cleavable linker, such as a peptidyl, disulfide, or hydrazone linker. In an aspect, a disclosed linker can be a peptidyl linker.

[0334] In an aspect, a disclosed ADC can be internalized into a TAS2R13-expressing cancer cell, whereupon the agent having cytotoxic and / or inhibitory and / or cytostatic activity is released into the cell. In an aspect, a disclosed ADC can be internalized into a TMEM191C-expressing cancer cell, whereupon the agent having cytotoxic and / or inhibitory and / or cytostatic activity is released into the cell. In an aspect, a disclosed ADC can be internalized into an ADAM20-expressing cancer cell, whereupon the agent having cytotoxic and / or inhibitory and / or cytostatic activity is released into the cell.

[0335] In an aspect, design of a disclosed ADC can consider target expression (e.g., Tumourspecific antigen against which the antibody is directed), target internalization (e.g., intracellular trafficking of the target antigen and the bound antibody-drug conjugate via receptor-mediated endocytosis), linker stability (e.g., covalent coupling of the cytotoxic drug to the antibody), conjugation (e.g., specific method of attachment of the cytotoxic drug and linker to the antibody), cytotoxic payload (e.g., type of cytotoxic drug that is conjugated to the antibody), or any combination thereof.4. Bispecific T Cell Engagers (BiTEs)

[0336] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv that binds to a TAS2R13 -expressing, TMEM191C-expressing, or ADAM20-expressing cancer cell, and (ii) a scFv that binds to a CD3. Bispecific T-cell engager molecules (BiTEs) constitute a class of bispecific single-chain antibodies for the polyclonal activation and redirection of cytotoxic T cells against pathogenic target cells (i.e., a cancer cell expressing TAS2R13, TMEM191C, or ADAM20). In an aspect, a disclosed BiTE is bispecific for a surface target antigen on cancer cells (i.e., TAS2R13, TMEM191C, or ADAM), and for CD3 on T cells. In an aspect, a disclosed BiTE can connect any kind of cytotoxic T cell to a cancer cell, independently of T-cell receptor specificity, costimulation, or peptide antigen presentation. In an aspect, a disclosed BiTE can have one or more advantages (such as, for example,extraordinary potency and efficacy against target cells at low T-cell numbers without the need for T-cell co-stimulation). In an aspect, activation of T cell activation can be confirmed by measuring the level of CD69 and / or CD25.

[0337] In an aspect, a disclosed BiTE can represent an interplay between immune effector cells and TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing tumor cells. In an aspect, a disclosed BiTE can be designed to engage immune cells and TAS2R13-expressing, TMEM191C-expressing, or ADAM20-expressing tumor cells simultaneously, targeting cytotoxicity within the tumor microenvironment. In an aspect, a disclosed BiTE can harbor dual specificity, binding to a TAS2R13 antigen, a TMEM191C antigen, or an ADAM20 antigen and an immune cell surface marker. In an aspect, engagement of T lymphocytes can lead to the formation of an immunological synapse and triggers the release of cytotoxic granules and proinflammatory cytokines, fostering a potent antitumor immune response. In an aspect, a disclosed BiTE can overcome immunosuppressive mechanisms within solid tumors, can enhance T-cell infiltration, can promote direct tumor cell killing, or any combination thereof.

[0338] In an aspect of a disclosed BiTE, the two disclosed scFvs can be connected with a linker such as a serine-glycine linker sequence. In an aspect, the length of a disclosed linker can determine the flexibility of movement between the disclosed two scFvs. In an aspect, a the length of a disclosed linker can be adjusted by including more or fewer repeats to optimize binding to both target cells.

[0339] In an aspect, a disclosed BiTE can comprise 1 continuous polypeptide. In an aspect, a disclosed BiTE can be approximately 50 kDa - 60 kDa in size. In an aspect, a disclosed BiTE can be approximately 55 kDa in size.

[0340] In an aspect of a disclosed BiTE, a disclosed VH sequence for a disclosed CD3 scFv can comprise the sequence set forth in any one of SEQ ID NO: 194 - SEQ ID NO:228.

[0341] In an aspect of a disclosed BiTE, a disclosed VH sequence for a disclosed CD3 scFv can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO: 194 - SEQ ID NO:228.

[0342] In an aspect of a disclosed BiTE, a disclosed VL sequence for a disclosed CD3 scFv can comprise the sequence set forth in any one of SEQ ID NO: 159 - SEQ ID NO: 193. In an aspect of a disclosed BiTE, a disclosed VL sequence for a disclosed CD3 scFv can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO: 159 - SEQ ID NO: 193.

[0343] In an aspect of a disclosed BiTE, a disclosed VH sequence for a disclosed CD3 scFv can comprise the sequence set forth in any one of SEQ ID NO: 194 - SEQ ID NO:228; and a disclosed VL sequence for a disclosed CD3 scFv can comprise the sequence set forth in any one of SEQ ID NO: 159 - SEQ ID NO: 193.

[0344] In an aspect of a disclosed BiTE, a disclosed VH sequence for a disclosed CD3 scFv can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO: 194 - SEQ ID NO:228; and a disclosed VL sequence for a disclosed CD3 scFv can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO: 159 - SEQ ID NO: 193.

[0345] In an aspect, a disclosed BiTE comprising a disclosed scFv targeting TAS2R13- expressing, TMEM191C-expressing, or ADAM20-expressing tumor cells can be used in a disclosed method of treating cancer and / or slowing disease progression in a subject. In an aspect, a disclosed BiTE comprising a disclosed scFv targeting TAS2R13-expressing, TMEM191C- expressing, or ADAM20-expressing tumor cells can be used in a disclosed method of stimulating an effector cell mediated immune modulator response in a subject.TAS2R13 #1

[0346] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising the sequence set forth in SEQ ID NO: 16 and (ii) a scFv that binds to a T cell marker.

[0347] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO: 16 and (ii) a scFv that binds to a T cell marker.

[0348] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by the sequence set forth in SEQ ID NO: 17 and (ii) a scFv that binds to a T cell marker.

[0349] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO: 17 and (ii) a scFv that binds to a T cell marker.

[0350] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by the sequence set forth in SEQ ID NO:203 and (ii) a scFv that binds to a T cell marker.

[0351] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%,at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO:203 and (ii) a scFv that binds to a T cell marker.

[0352] In an aspect, a disclosed scFv can comprise the sequence of SEQ ID NO: 129, but for NT 1-6 and NT 766-774, which are restriction sites.

[0353] TAS2R13 is discussed herein. TAS2R13 antigen is discussed herein.

[0354] In an aspect, a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO: 15. In an aspect, a disclosed sequence encoding a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed sequence encoding a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO: 16. The amino acid sequences and nucleotide sequences of disclosed signal peptides are disclosed herein.

[0355] In an aspect of a disclosed BiTE, a disclosed scFv that binds to TAS2R13 -expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the constant heavy chain region.

[0356] In an aspect of a disclosed BiTE, a disclosed scFv that binds to TAS2R13 -expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0357] In an aspect of a disclosed BiTE targeting TAS2R13, a disclosed VH of a disclosed scFV can comprise the sequence set forth in SEQ ID NO:20 or a fragment thereof. In an aspect of a disclosed BiTE, a disclosed VH of a disclosed scFV can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:20. In an aspect of a disclosed BiTE, a disclosed VH of a disclosed scFV can be encoded by the sequence set forth in SEQ ID NO:21 or a fragment thereof. In an aspect of a disclosed BiTE, a disclosed VH of a disclosed scFV can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:21.

[0358] In an aspect of a disclosed BiTE targeting TAS2R13, a disclosed VL of a disclosed scFV can comprise the sequence set forth in SEQ ID NO:22 or a fragment thereof. In an aspect of a disclosed BiTE, a disclosed VL of a disclosed scFV can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:22. In an aspect of a disclosed BiTE, a disclosed VL of adisclosed scFV of a disclosed scFV can be encoded by the sequence set forth in SEQ ID NO:23 or a fragment thereof. In an aspect of a disclosed BiTE, a disclosed VL of a disclosed scFV can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:23.

[0359] In an aspect of a disclosed BiTE targeting TAS2R13, a disclosed VH of a disclosed scFV can comprise three complementarity determining regions (CDRs). In an aspect of a disclosed scFv that binds to TAS2R13 -expressing cancer cells, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:06, and SEQ ID NO:07. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:07, and SEQ ID NO:07.

[0360] In an aspect of a disclosed BiTE targeting TAS2R13, a disclosed VL of a disclosed scFV can comprise three complementarity determining regions (CDRs). In an aspect of a disclosed scFv that binds to TAS2R13 -expressing cancer cells, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13.

[0361] In an aspect of a disclosed scFv that binds to TAS2R 13 -expressing cancer cells, a disclosed CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect of a disclosed scFv that binds to TAS2R 13 -expressing cancer cells, a disclosed CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed CDR comprising 13 amino acids can comprise 3 or more substitutions.

[0362] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed CDR comprising the sequence set forth in SEQ ID NO:09 can further comprise 1 or more substitutions. In an aspect of a disclosed scFv that binds to TAS2R13- expressing cancer cells, a disclosed CDR comprising the sequence set forth in SEQ ID NO:02 and / or SEQ ID NO:03 can further comprise 1 or more substitutions. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed CDR comprising the sequence set forth in SEQ ID NO:08 and / or SEQ ID NO: 10 can further comprise 1 or more substitutions. In an aspect of a disclosed scFv that binds to TAS2R 13 -expressing cancer cells, a disclosed CDR comprising the sequence set forth in SEQ ID NO:04 can further comprise 3 or more substitutions.

[0363] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect of a disclosed scFv that binds to TAS2R 13 -expressing cancer cells, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04. In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and SEQ ID NO:04.

[0364] In an aspect of a disclosed BiTE targeting TAS2R13, a disclosed VL of a disclosed scFV can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect of a disclosed BiTE, a disclosed VL of a disclosed scFV can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO: 08, SEQ ID NO: 09, and SEQ ID NO: 10. In an aspect of a disclosed BiTE, a disclosed VL of a disclosed scFV can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10. In an aspect of a disclosed BiTE, a disclosed VL of a disclosed scFV can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and SEQ ID NO: 10.

[0365] In an aspect of a disclosed BiTE that binds to TAS2R13-expressing cancer cells, a disclosed scFv can comprise a variation in the order of a disclosed VH, a disclosed linker, and a disclosed VL. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VH, a disclosed linker, and a disclosed VL in this order. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VL, a disclosed linker, and a disclosed VH in this order.

[0366] In an aspect of disclosed BiTE, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by the sequence set forth in SEQ ID NO:21, a disclosed linker, and a VL encoded by the sequence set forth in SEQ ID NO:23. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:21, a disclosed linker, and a VL encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:23.

[0367] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed CDR can be a CDR set forth in Table 1.

[0368] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising the sequence set forth in SEQ ID NO:38 and (ii) a scFv that binds to a T cell marker.

[0369] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO:38 and (ii) a scFv that binds to a T cell marker.

[0370] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by the sequence set forth in SEQ ID NO:39 or SEQ ID NO: 127 and (ii) a scFv that binds to a T cell marker.

[0371] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO:39 or SEQ ID NO: 127 and (ii) a scFv that binds to a T cell marker.

[0372] In an aspect of a disclosed BiTE targeting TAS2R13, a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO:36. In an aspect, a disclosed sequence encoding a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed sequence encoding a disclosed scFvcomprising a signal peptide can comprise the sequence set forth in SEQ ID NO:37. The amino acid sequences and nucleotide sequences of disclosed signal peptides are disclosed herein.

[0373] In an aspect of a disclosed BiTE, a disclosed scFv that binds to TAS2R13 -expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs) and a conserved region, and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the constant heavy chain region. In an aspect of a disclosed BiTE, a disclosed scFv that binds to TAS2R13- expressing cancer cells can comprise (i) a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs), and (ii) a variable heavy chain region (VH) comprising 3 CDRs and a conserved heavy chain region, wherein the VH is linked to the conserved heavy chain region.

[0374] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed VH can comprise the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:43. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43.

[0375] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed VL can comprise the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.

[0376] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH- CDR can be encoded by the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, andSEQ ID NO:32. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32.

[0377] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL- CDR can be encoded by the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35.

[0378] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 10 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0379] In an aspect of a disclosed scFv that binds to TAS2R13-expressing cancer cells in a disclosed BiTE, a disclosed CDR comprising the sequence set forth in SEQ ID NO:28 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, and / or SEQ ID NO:29, and / or any combination thereof can further comprise 2 or more substitutions. In an aspect, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from thesequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and SEQ ID NO:29.

[0380] In an aspect of a disclosed BiTE that binds to TAS2R13-expressing cancer cells, a disclosed VL can be located at the N-terminus of the VH. In an aspect, a disclosed extracellular domain comprising a TAS2R13 binding domain can comprise SEQ ID NO: 42 and SEQ ID NO: 44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising the sequence set forth in SEQ ID NO:44. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:42, a disclosed linker, and a VL comprising a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:44.

[0381] In an aspect of a disclosed BiTE that binds to TAS2R13-expressing cancer cells, a disclosed scFv comprising a TAS2R13 binding domain can comprise a variation in the order of a disclosed VH, a disclosed linker, and a disclosed VL. In an aspect of a disclosed BiTE that binds to TAS2R13-expressing cancer cells, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VH, a disclosed linker, and a disclosed VL in this order. In an aspect of a disclosed BiTE that binds to TAS2R13-expressing cancer cells, a disclosed scFv comprising a TAS2R13 binding domain can comprise a disclosed VL, a disclosed linker, and a disclosed VH in this order.

[0382] In an aspect of a disclosed BiTE that binds to TAS2R13-expressing cancer cells, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed scFv comprising a TAS2R13 binding domain can comprise a VH encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:43, a disclosed linker, and a VL encoded by a sequence having at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:45.

[0383] In an aspect, the following can be applied to a disclosed scFv that binds to TAS2R13- expressing cancer cells in a disclosed BiTE, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity. In an aspect of a disclosed scFv that binds to TAS2R13 -expressing cancer cells in a disclosed BiTE, a disclosed CDR can be set forth in Table 2.TMEM191C

[0384] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising the sequence set forth in SEQ ID NO:89 and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO:89 and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by the sequence set forth in SEQ ID NO:90 and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO: 90 and (ii) a scFv that binds to a T cell marker.

[0385] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VH can comprise the sequence set forth in SEQ ID NO:83. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 83. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:84. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:84.

[0386] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VL can comprise the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:85. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:86. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, atleast 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:86.

[0387] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VH can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH-CDR can comprise the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 72, SEQ ID NO:73, and SEQ ID NO:74.

[0388] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VL can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL-CDR can comprise the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 78, SEQ ID NO: 79, and SEQ ID NO: 80.

[0389] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VH-CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 10 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VH-CDR comprising 11 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VL-CDR comprising 8 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 9 amino acids can comprise 2 or more substitutions.

[0390] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed CDR comprising the sequence set forth in SEQ ID NO:76 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:75 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprisingthe sequence set forth in SEQ ID NO:70 and / or SEQ ID NO:77 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:69 can further comprise 2 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:71SEQ ID NO:71 can further comprise 3 or more substitutions.

[0391] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VH can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO : 69 SEQ ID NO : 71 SEQ ID NO : 71 SEQ ID NO : 69, SEQ ID NO : 70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71 SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:69SEQ ID NO:71SEQ ID NO:71SEQ ID NO:69, SEQ ID NO:70, and SEQ ID NO:71. In an aspect, a disclosed VL can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.

[0392] In an aspect of a disclosed BiTE comprising a disclosed scFv targeting TMEM191C, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:75SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO: 75 SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.

[0393] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0394] In an aspect of a disclosed scFv that binds to TMEM191C-expressing cancer cells in a disclosed BiTE, a disclosed CDR can be a CDR set forth in Table 3.ADAM20

[0395] Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprising the sequence set forth in SEQ ID NO:60 and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv comprisinga sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO:60 and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by the sequence set forth in SEQ ID NO:61 and (ii) a scFv that binds to a T cell marker. Disclosed herein is a bispecific T cell engager (BiTE) comprising (i) a disclosed scFv encoded by a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% to the sequence set forth in SEQ ID NO:61 and (ii) a scFv that binds to a T cell marker.

[0396] In an aspect, a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO:58.

[0397] In an aspect, a disclosed sequence encoding a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed sequence encoding a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO: 59. ADAM20 is discussed herein. ADAM20 antigen is discuss herein.

[0398] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO:58. In an aspect, a disclosed sequence encoding a disclosed scFv can comprise a signal peptide. In an aspect, a disclosed sequence encoding a disclosed scFv comprising a signal peptide can comprise the sequence set forth in SEQ ID NO:59. The amino acid sequences and nucleotide sequences of disclosed signal peptides are disclosed herein.

[0399] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VH of a disclosed scFv can comprise the sequence set forth in SEQ ID NO:64. In an aspect, a disclosed VH can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 64. In an aspect, a disclosed VH can be encoded by the sequence set forth in SEQ ID NO:65. In an aspect, a disclosed VH can be encoded by a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:65.

[0400] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VL of a disclosed scFv can comprise can comprise the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can comprise a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:66. In an aspect, a disclosed VL can be encoded by the sequence set forth in SEQ ID NO:67. In an aspect, a disclosed VL can be encoded by a sequence having at least 70%, at least 75%, at least 80%, atleast 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:67.

[0401] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VH of a disclosed scFv can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VH- CDR can comprise the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54. In an aspect, a disclosed VH-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54.

[0402] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VL of a disclosed scFv can comprise three complementarity determining regions (CDRs). In an aspect, a disclosed VL- CDR can comprise the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL-CDR can be encoded by the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57. In an aspect, a disclosed VL-CDR can be encoded by a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:55, SEQ ID NO:56, and SEQ ID NO:57.

[0403] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VH-CDR comprising 8 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VH-CDR comprising 14 amino acids can comprise 3 or more substitutions. In an aspect, a disclosed VL-CDR comprising 3 amino acids can comprise 1 or more substitutions. In an aspect, a disclosed VL- CDR comprising 9 amino acids can comprise 2 or more substitutions. In an aspect, a disclosed VL-CDR comprising 10 amino acids can comprise 2 or more substitutions.

[0404] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed CDR comprising the sequence set forth in SEQ ID NO:74 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:46 or SEQ ID NO:47 can further comprise 1 or more substitutions. In an aspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:49 or SEQ ID NO:51 can further comprise 2 or more substitutions. In anaspect, a disclosed CDR comprising the sequence set forth in SEQ ID NO:48 can further comprise 3 or more substitutions.

[0405] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VH of a disclosed scFv can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. In an aspect, a disclosed VH can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48.

[0406] In an aspect of a disclosed BiTE targeting ADAM20, a disclosed VL of a disclosed scFv can comprise a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise one or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise two or more CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:51. In an aspect, a disclosed VL can comprise three CDRs that are evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, and SEQ ID NO:5L

[0407] In an aspect, choosing the amino acid substitutions for a disclosed CDR can be informed by Gonzalez-Munoz et al. (2012) MAbs. 4(6):664-672, which is incorporated herein in its entirety for its teaching of tailoring amino acid diversity for the evolution of antibody affinity.

[0408] In an aspect, a disclosed extracellular domain comprising a ADAM20 binding domain can comprise SEQ ID NO:64 and SEQ ID NO:66. In an aspect of a disclosed scFv that binds to ADAM20-expressing cancer cells in a disclosed BiTE, a disclosed CDR can be a CDR set forth in Table 4.5. Nucleic Acid Molecules

[0409] Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed antibody, a disclosed ADC, or a disclosed BiTE. Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20. Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed ADC comprising a disclosed antibody targeting TAS2R13, TMEM191C, or ADAM20. Disclosed herein is a nucleic acid sequence encoding a disclosedBiTE comprising an antibody targeting TAS2R13, TMEM191C, or ADAM20. Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed single-chain fragment variant (scFv) targeting TAS2R13, TMEM191C, or ADAM20.

[0410] In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13, TMEM191C, ADAM20, or any combination thereof. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TMEM191C. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target ADAM20. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13, TMEM191C, ADAM20, or any combination thereof expressed on the cell surface of a cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13 expressed on the cell surface of a cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TMEM191C expressed on the cell surface of a cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target ADAM20 expressed on the cell surface of a cancer cell.

[0411] In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13, TMEM191C, ADAM20, or any combination thereof expressed on the cell surface of a lung cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13, TMEM191C, ADAM20, or any combination thereof expressed on the cell surface of a lung cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TAS2R13 expressed on the cell surface of a lung cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target TMEM191C expressed on the cell surface of a lung cancer cell. In an aspect, an antibody encoded by a disclosed nucleic acid sequence can target ADAM20 expressed on the cell surface of a lung cancer cell.

[0412] Disclosed herein is a nucleic acid molecule encoding an antibody comprising a VL comprising an antigen binding domain targeting TAS2R13, TMEM191C, or ADAM20 and a VH. Disclosed herein is a nucleic acid molecule encoding a scFV comprising a VL comprising an antigen binding domain targeting TAS2R13, TMEM191C, or ADAM20 and a VH.TAS2R13

[0413] Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed antibody targeting TAS2R13. Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed scFv targeting TAS2R13.

[0414] In an aspect of a disclosed nucleic acid molecule, a CDR can be encoded by the sequence set forth in any one SEQ ID NO:05 - SEQ ID NO:08 or SEQ ID NO: 11 - SEQ ID NO: 13. In anaspect, SEQ ID NO:05 can encode a disclosed CDR. In an aspect, SEQ ID NO:06 can encode a disclosed CDR. In an aspect, SEQ ID NO:07 can encode a disclosed CDR. In an aspect, SEQ ID NO: 11 can encode a disclosed CDR. In an aspect, SEQ ID NO: 12 can encode a disclosed CDR. In an aspect, SEQ ID NO: 13 can encode a disclosed CDR.

[0415] In an aspect, SEQ ID NO:05 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:06 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:07 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO: 11 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO: 12 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO: 13 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:05 can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:05. In an aspect, SEQ ID NO:06 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO: 03. In an aspect, SEQ ID NO: 07 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:04. In an aspect, SEQ ID NO: 11 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO: 08. In an aspect, SEQ ID NO: 12 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:09. In an aspect, SEQ ID NO: 13 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO: 10.

[0416] In an aspect, a disclosed nucleic acid molecule can comprise a nucleic acid sequence encoding a TAS2R13 binding domain. In an aspect, a disclosed TAS2R13 binding domain can comprise a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs) and a light chain variable region (VL) comprising three complementarity determining regions (CDRs).

[0417] In an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in the VH can comprise the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:06, and SEQ ID NO:07. In an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in the VH can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:05, SEQ ID NO:06, and SEQ ID NO:07.

[0418] In an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in theVL can comprise the nucleic acid sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13. In an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in the VL can comprise a nucleic acid sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13.

[0419] In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise the sequence set forth in SEQ ID NO: 19. In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in in SEQ ID NO: 19. In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise the sequence set forth in SEQ ID NO:21. In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in in SEQ ID NO:21. In an aspect, a disclosed nucleic acid encoding a disclosed VL can comprise the sequence set forth in SEQ ID NO:23. In an aspect, a disclosed nucleic acid encoding a disclosed VL can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in in SEQ ID NO:23.

[0420] In an aspect, a disclosed nucleic acid molecule can encode a CDR comprising the sequence set forth in SEQ ID NO:09 with 1 or more substitutions. In an aspect, a disclosed nucleic acid molecule can encode a CDR comprising the sequence set forth in SEQ ID NO:02, SEQ ID NO:03, SEQ ID NO:08, and / or SEQ ID NO: 10 with 2 or more substitutions. In an aspect, a disclosed nucleic acid molecule can encode a CDR comprising the sequence set forth in SEQ ID NO:04 with 3 or more substitutions. In an aspect, a disclosed nucleic acid molecule can comprise a sequence encoding a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, and / or SEQ ID NO:04. In an aspect, a disclosed nucleic acid molecule can comprise a sequence encoding a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, and / or SEQ ID NO: 10.

[0421] In an aspect, a nucleic acid molecule comprising the sequence set forth in SEQ ID NO: 15 can encode a disclosed scFv (with a signal peptide) comprising the sequence set forth in SEQ ID NO: 14. In an aspect, a nucleic acid molecule comprising the sequence set forth in SEQ ID NO: 17 can encode a disclosed scFv (without a signal peptide) comprising the sequence set forth in SEQ ID N0: 16.

[0422] In an aspect, a disclosed scFv can comprise the sequence set forth in SEQ ID NO: 126, but for NTs 1-6 and NT 759-768, which are restriction sites. In an aspect, a disclosed scFv can comprise the sequence set forth in SEQ ID NO: 127, but for NTs 1-6 and NT 751-759, which arerestriction sites. In an aspect, a disclosed scFv can comprise the sequence set forth in SEQ ID NO: 128.

[0423] In an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in the VH can comprise the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32. In an aspect of a disclosed nucleic acid molecule, a disclosed CDR in the VH can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32.

[0424] In an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in the VL can comprise the nucleic acid sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35. n an aspect, a disclosed nucleic acid molecule encoding a disclosed CDR in the VL can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in any one of SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:35. In an aspect of a disclosed nucleic acid molecule, a CDR can be encoded by the sequence set forth in any one SEQ ID NO:30 - SEQ ID NO:35. In an aspect, SEQ ID NO:30 can encode a disclosed CDR. In an aspect, SEQ ID NO:31 can encode a disclosed CDR. In an aspect, SEQ ID NO:32 can encode a disclosed CDR. In an aspect, SEQ ID NO:33 can encode a disclosed CDR. In an aspect, SEQ ID NO:34 can encode a disclosed CDR. In an aspect, SEQ ID NO:35 can encode a disclosed CDR.

[0425] In an aspect, SEQ ID NO:30 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:31 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:32 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:33 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:34 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:35 can comprise one or more nucleotide substitutions. In an aspect, SEQ ID NO:36 can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:24. In an aspect, SEQ ID NO:30 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:25. In an aspect, SEQ ID NO:32 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:26. In an aspect, SEQ ID NO:33 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:27. In an aspect, SEQ ID NO:34 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutionsthereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:28. In an aspect, SEQ ID NO:35 can comprise one or more nucleotide substitutions can comprise one or more nucleotide substitutions thereby causing the encoded CDR to differ by at least 20% from the sequence set forth in SEQ ID NO:29.

[0426] In an aspect, a disclosed nucleic acid molecule can encode a CDR comprising the sequence set forth in SEQ ID NO:28 with 1 or more substitutions. In an aspect, a disclosed nucleic acid molecule can encode a CDR comprising the sequence set forth in SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, and / or SEQ ID NO:29 with 2 or more substitutions. In an aspect, a disclosed nucleic acid molecule can comprise a sequence encoding a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:24, SEQ ID NO:25, and / or SEQ ID NO:26. In an aspect, a disclosed nucleic acid molecule can comprise a sequence encoding a CDR that is evolved to differ by at least 20% from the sequence set forth in any one of SEQ ID NO:27, SEQ ID NO:28, and / or SEQ ID NO:29.

[0427] In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise the sequence set forth in SEQ ID NO:41. In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in in SEQ ID NO:41. In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise the sequence set forth in SEQ ID NO:43. In an aspect, a disclosed nucleic acid encoding a disclosed VH can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in in SEQ ID NO:43. In an aspect, a disclosed nucleic acid encoding a disclosed VL can comprise the sequence set forth in SEQ ID NO:45. In an aspect, a disclosed nucleic acid encoding a disclosed VL can comprise a sequence having at least 70%, at least 75%, or at least 80% identity to the sequence set forth in in SEQ ID NO:45.

[0428] In an aspect, a nucleic acid molecule comprising the sequence set forth in SEQ ID NO:37 can encode a disclosed scFv (with a signal peptide) comprising the sequence set forth in SEQ ID NO:36. In an aspect, a nucleic acid molecule comprising the sequence set forth in SEQ ID NO:39 can encode a disclosed scFv (without a signal peptide) comprising the sequence set forth in SEQ ID NO:38.TMEM191C

[0429] Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed antibody targeting TMEM191C. Disclosed herein is a nucleic acid molecule comprising a nucleic acid sequence encoding a disclosed scFv targeting TMEM191C.

[0430] In an aspect of a disclosed nucleic acid molecule, a CDR can be encoded by the sequence set forth in any one SEQ ID NO:72 - SEQ ID NO:74 or SEQ ID NO:78 - SEQ ID NO:80. In anaspect, SEQ ID NO:72 can encode a disclosed CDR. In an aspect, SEQ ID NO:73 can encode a disclosed C...

Claims

1. VIII. CLAIMSWhat is claimed is:

1. An anti-TAS2R13 antibody, comprising: a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs); a variable heavy chain region (VH) comprising 3 CDRs, wherein the VL is linked to the VH.

2. The anti-TAS2R13 antibody of Claim 1, wherein wherein each CDR in the VH comprise the sequence set forth in any one of SEQ ID NO:02, SEQ ID NO:03, SEQ ID NO:04, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26; and wherein each CDR in the VL comprise the sequence set forth in any one of SEQ ID NO:08, SEQ ID NO:09, SEQ ID NO: 10, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.

3. An anti-TMEM191C antibody, comprising: a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs); and a variable heavy chain region (VH) comprising 3 CDRs, wherein the VL is linked to the VH.

4. The anti-TMEM191C antibody of Claim 3, wherein wherein each CDR in the VH comprise the sequence set forth in any one of SEQ ID NO:69, SEQ ID NO:70, or SEQ ID NO:71; and wherein each CDR in the VL comprise the sequence set forth in any one of SEQ ID NO:75, SEQ ID NO:76, or SEQ ID NO:77.

5. An anti-ADAM20 antibody, comprising: a variable light chain region (VL) comprising 3 complementarity determining regions (CDRs); and a variable heavy chain region (VH) comprising 3 CDRs, wherein the VL is linked to the VH.

6. The anti-ADAM20 antibody of Claim 3, wherein wherein each CDR in the VH comprise the sequence set forth in any one of SEQ ID NO:46, SEQ ID NO:47, or SEQ ID NO:48; and wherein each CDR in the VL comprise the sequence set forth in any one of SEQ ID NO:49, SEQ ID NO:50, or SEQ ID NO:51.

7. The antibody of any one of Claims 1 - 6, wherein the linker comprises the sequence set forth inSEQ ID NO: 108 or SEQ ID NO: 110.

8. A single chain variable fragment (scFv) recognizing TAS2R13 and comprising the sequence set forth in SEQ ID NO: 16 or SEQ ID NO:38.

9. A single chain variable fragment (scFv) recognizing TMEM191C and comprising the sequence set forth in SEQ ID NO:89.

10. A single chain variable fragment (scFv) recognizing ADAM20 and comprising the sequence set forth in SEQ ID NO: 60.

11. An antibody drug conjugate, comprising: the antibody of any one of Claims 1 - 7 conjugated to an agent having cytotoxic and / or inhibitory and / or cytostatic activity12. A bispecific T cell engager (BiTE), comprising: (i) the scFv of any one of Claims 8 - 10; and(ii) a scFv that binds to a T cell marker.

13. The BiTE of Claim 12, wherein the scFv that binds to the T cell marker comprises (i) a VH sequence comprising the sequence set forth in any one of SEQ ID NO: 194 - SEQ ID NO:228 and (ii) a VL sequence comprising the sequence set forth in any one of SEQ ID NO: 159 - SEQ ID NO: 193.

14. A nucleic acid molecule encoding the antibody of any one of Claims 1 - 7.

15. A nucleic acid molecule encoding the scFv of any one of Claims 8 - 10.

16. A pharmaceutical formulation, comprising: the anti-TAS2R13 antibody of any Claims 1 or 2; the anti-TMEM191C antibody of Claims 3 or 4; the anti-ADAM20 antibody of Claims 5 or 6; the ADC of Claim 11; the BiTE of Claims 12 or 13; and one or more pharmaceutically acceptable carriers.

17. A method of treating cancer and / or slowing disease progression, the method comprising: administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical formulation of Claim 15, wherein, following the administering step, (i) the subject’s cancer is treated, (ii) one or more symptoms associated with the subject’s cancer are attenuated, ameliorated, or eliminated, (iii) one or more symptoms of the subject’s cancer are delayed.

18. The method of Claim 17, further comprising stimulating an effector cell mediated immune modulator response to TAS2R13, TMEM191C, and / or ADAM20-expressing tumor cells.

19. The method of Claim 17, further comprising administering to the subject one or more additional anti -cancer therapies.

20. The method of Claim 19, wherein the one or more anti-cancer therapies comprises endocrine therapy, radiotherapy, hormone therapy, gene therapy, thermal therapy, ultrasound therapy, or any combination thereof.

Images