Compositions comprising an interleukin and a calcium compound for treating a cancer

Abstract

Provided herein are polypeptides comprising a therapeutic targeted for delivery to an organ or tissue, and uses thereof.

Description

[0001] COMPOSITIONS AND METHODS FOR LOCALIZATION OF IMMUNOMODULATOR ACTIVITY

[0002] CROSS-REFERENCE

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 505,026 filed on May 30, 2023, which is incorporated herein by reference in its entirety.

[0004] SEQUENCE LISTING

[0005] The application contains a Sequence Listing, which is submitted herewith in XML format, and is hereby incorporated by reference in its entirety. The XML copy, created on May 29, 2024, is named 50222-712_601.xml and is 122,650 bytes in size.

[0006] BACKGROUND

[0007] Cytokines are effective in activating the immune system and may be used as immunomodulators to stimulate the immune system for the treatment of cancer. However, systemic administration of cytokines elicits severe side effects that limit wider use.

[0008] SUMMARY

[0009] In various aspects, provided herein are immunomodulator compositions and systems for the treatment of cancer. In various embodiments, the immunomodulator is localized to the cancer of the subject to reduce or eliminate systemic side effects associated with systemic delivery of the immunomodulator without localization. Example compositions and systems include variant interleukins, variant human leukocyte antigen (HLA) receptors (also referred to as major histocompatibility complex receptors), tumor antigen peptides, and combinations thereof. Various embodiments comprise a particle, wherein the variant interleukin and / or variable HLA are tethered to the particle. The variant HLA may be combined with the tumor antigen peptide. The compositions and systems may be delivered systemically.

[0010] Provided herein are methods of activating an immune response and / or treating cancer in a subject in need thereof, the methods comprising delivering to the subject an immunomodulatory polypeptide comprising an interleukin, and a particle comprising a calcium compound. In some embodiments, the immunomodulatory polypeptide comprises a binding peptide that binds the calcium compound of the particle. In some embodiments, the binding peptide comprises a sequence at least 80% identical to any one of SEQ ID NOS: 12-14 and 1-11. In some embodiments, the immunomodulatory polypeptide comprises a protease cleavage site positioned between the interleukin and the binding peptide, wherein the protease cleavage site is cleaved by a protease of a T cell and / or a cancer cell. In some embodiments, the protease cleavage site comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113. In some embodiments, the immunomodulatory polypeptide comprises a linker positioned between the interleukin and the binding peptide, wherein the linker comprises (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111, (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105; or (iii) one or more of SEQ ID NOS: 36-52, 101-113, and 124-125. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 16, 15, and 94-100. In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the immunomodulatory polypeptide is localized to a target site in the subject, the immunomodulatory polypeptide does not result in systemic activation of the immune response, delivering to the subject results in fewer side effects than delivery to the subject the immunomodulatory polypeptide without the particle, and / or the method results in immune activation that is specific for the cancer. In some embodiments, the method comprises administering to the subject an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor comprises an anti-PDl antibody. In some embodiments, the cancer is melanoma, renal cell carcinoma, pancreatic, colorectal, lung, kidney, liver, uterine, bladder, thyroid, ovarian, or breast cancer. In some embodiments, the delivery is via intratumoral (IT) injection, guided injection to a lymph node, subcutaneous, intramuscular, or tumor embolization via venous catheter. In some embodiments, the delivery is performed during a surgical procedure, a colonoscopy, or an endoscopy. In some embodiments, the particle is from about 1 micron to about 100 microns in size. In some embodiments, the calcium compound comprises beta-tricalcium phosphate.

[0011] Provided herein are composition comprising a calcium compound particle, and a peptide fusion protein comprising a binding peptide connected to an immunomodulatory polypeptide, wherein the binding peptide binds to the calcium compound to tether the peptide fusion protein to the calcium compound particle, optionally wherein the immunomodulatory polypeptide comprises an interleukin (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF -related apoptosis-inducing ligand (TRAIL), or Interleukin 4 (IL4). In some embodiments, the binding peptide comprises one or more of: a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 12-14 and 1-11. In some embodiments, the immunomodulatory polypeptide comprises the interleukin, and the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the immunomodulatory polypeptide comprises the interleukin, and the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 16, 15 and 94-100. In some embodiments, the composition comprises a linker position between the binding peptide and the immunomodulatory polypeptide, wherein the linker comprises (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111, (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104; or (iii) one or more of SEQ ID NOS: 36-52, 101-113, and 124-125. In some embodiments, the composition comprises a protease cleavage site positioned between the binding peptide and the immunomodulatory polypeptide, wherein the protease cleavage site comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase (MMP) cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113. In some embodiments, the particle is from about 1 micron to about 100 microns in size. In some embodiments, the calcium compound comprises beta-tricalcium phosphate.

[0012] Provided herein are fusion proteins of Formula 1, Formula 2, Formula 3, Formula 4, Formula 5, Formula 6, Formula 7, Formula 8, Formula 9, Formula 10, Formula 11, or Formula 12:

[0013] TA - BP (Formula 1), TA - L - BP (Formula 2), BP - TA (Formula 3), BP - L - TA (Formula 4), TAI - LI - BP - L2 - TA2 (Formula 5), TAI - BP - TA2 (Formula 6), TAI - LI - BP - TA2 (Formula 7), TAI - BP - LI - TA2 (Formula 8) BP1 - LI - TA - L2 - BP2 (Formula 9), BP 1 - TA - BP2 (Formula 10),

[0014] BP1 - LI - TA - BP2 (Formula 11),

[0015] BP1 - TA - LI - BP2 (Formula 12); wherein each TA, TAI, and TA2 is independently a therapeutic agent; each L, LI, and L2 is independently a linker, and each BP, BP1, and BP2 is independently a binding peptide; and wherein: each therapeutic agent independently comprises: an immunomodulatory agent, an anti -cancer agent, an antigen peptide, or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 15-23, 53, 58-100, and 122; each binding peptide independently comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14; and each linker independently comprises one or more of: (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 36-52, 101-113, 127-128, and 124-125.

[0016] Provided herein are polypeptides comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 24, 114, 25-35, 54-57, 126, and 115-121.

[0017] Provided herein are polypeptides comprising (i) a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS), and (ii) an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT).

[0018] Provided herein are polypeptides comprising (i) a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13 (AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAE STSKKRPFS), and (ii) an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT). Provided herein are polypeptides comprising:

[0019] (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16

[0020] (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCL EEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR WITFSQSIISTLT); and

[0021] (ii)

[0022] (a) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0023] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1

[0024] (ILAETTHHRPWS),

[0025] (b) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2 (STADTSHHRPST),

[0026] (c) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3 (VGADSTHHRPVT),

[0027] (d) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4 (LIADSTHHSPWT),

[0028] (e) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5 (AAESTSKKRPFS),

[0029] (f) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7 (VIGESTHHRPWS),

[0030] (g) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10 (ILAESTHHKPWT),

[0031] (h) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8 (IIGESSHHKPFT),

[0032] (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9 (GLGDTTHHRPWG),

[0033] (j) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6 (LLADTTHHRPWT), (k) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0034] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11,

[0035] (l) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0036] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12,

[0037] (m) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0038] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13,

[0039] (n) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14, or

[0040] (o) a combination comprising two or more sequences of (a)-(n).

[0041] In some embodiments of the polypeptides herein, the polypeptides comprise a linker positioned between (i) and (ii), wherein the linker comprises (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0042] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111,

[0043] (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%.

[0044] 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103, a sequence at least 80%,

[0045] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0046] 98%, or 99% identical to SEQ ID NO: 43, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105; or (iii) one or more of SEQ ID NOS: 36-52, 101-113, and 124-125.

[0047] In some embodiments of the polypeptides herein, the polypeptides comprise a protease cleavage site positioned between (i) and (ii), wherein the protease cleavage site comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113. In some embodiments, the cleavable linker comprises SEQ ID NO: 106 (RKKR) or SEQ ID NO: 113 (RKKRSTDEVDGAPPLGL).

[0048] Provided herein are polypeptides comprising (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13

[0049] (AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAE STSKKRPFS), (ii) a first interleukin-2, and (iii) a second interleukin-2, wherein each of the first interleukin-2 and the second interleukin-2 independently comprise a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16

[0050] (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT). In some embodiments, (i) is positioned between (ii) the first interleukin-2 and (iii) the second interleukin-2. In some embodiments, (i) and (ii) are connected via a first linker, and (i) and (iii) are connected via a second linker. In some embodiments, the first linker comprises one or more of SEQ ID NOS: 36-52, 124-125, and 101-113, and the second linker comprises one or more of SEQ ID NOS: 36-52, 124-125, 101-113. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more of SEQ ID NOS: 103, 109, and 104; and the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more of SEQ ID NOS: 103, 109, and 104. In some embodiments, the first linker comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113; and the second linker comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113. In some embodiments, the first linker comprises a furin cleavage site and the second linker comprises a furin cleavage site.

[0051] Provided herein are polypeptides comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13 (AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAE STSKKRPFS), SEQ ID NO: 12 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS), or SEQ ID NO: 14 (LIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIA DSTHHSPWT).

[0052] Provided herein are nucleic acids encoding a composition herein, a fusion protein herein, or a polypeptide herein. Provided herein are vectors comprising the nucleic acids herein.

[0053] Provided herein are kits comprising a composition herein, a fusion protein herein, or a polypeptide herein, and a particle comprising a calcium compound.

[0054] Provided herein are methods of treating a subject in need thereof, the methods comprising delivering to the subject a composition herein, a fusion protein herein, a polypeptide herein, or a kit herein. The methods may comprise administering to the subject an immune checkpoint inhibitor. The immune checkpoint inhibitor may comprise an anti-PDl antibody. The method of treating may comprise treating cancer in the subject, wherein the cancer is melanoma, renal cell carcinoma, pancreatic, colorectal, lung, kidney, liver, uterine, bladder, thyroid, ovarian, or breast cancer. The method of treating may comprise activating an immune response in the subject. The delivery may be via intratumoral (IT) injection, guided injection to a lymph node, subcutaneous, intramuscular, or tumor embolization via venous catheter. The delivery may be performed during a surgical procedure, a colonoscopy, or an endoscopy.

[0055] DESCRIPTION OF DRAWINGS

[0056] FIG. 1 depicts a diagram of the treatment of a patient with a cancer by injecting a TCP (tricalcium phosphate) particle tethered with a variant IL-2 peptide and a variant HLA-A peptide, wherein the variant HLA-A peptide is bound with a neoantigen peptide (NA123; SEQ ID NO: 123 NGFEQARDC).

[0057] FIG. 2 depicts the engineering process of designing a carrier particle and a variant IL-2 peptide, attaching the IL-2 peptide to the carrier, and preparing the construct for delivery as a treatment.

[0058] FIG. 3 depicts the engineering process of designing a carrier particle, a variant IL-2 peptide, and a variant HLA fusion peptide, attaching the variant IL-2 peptide and variant HLA fusion peptide to the carrier, combining with a neoantigen peptide to generate a neoantigen-peptide loaded particle, and delivering the loaded particle as a treatment.

[0059] FIG. 4 depicts the results of a protein refolding experiment for ILX-1, ILX-2, ILX-3, ILX-4, ILX-5, ILX-6, ILX-7, and ILX-8 labeled as lanes 1-8 respectively.

[0060] FIG. 5 depicts the testing of ILX-1, ILX-4, ILX-5, and ILX-7 for their solubility in PBS by running an SDS-PAGE gel on the dialysates after centrifugation.

[0061] FIG. 6 depicts the response of CTLL-2 cells, which respond to IL2 activity, to increasing doses of ILX-1, ILX-4, ILX-5, and ILX-7 versus a control. Proliferation of the CTLL-2 cells was assessed using AlamarBlue reagent.

[0062] FIG. 7 depicts an assay showing the ability of ILX-1, ILX-4, ILX-5, and ILX-7 to bind to bTCP (beta-tricalcium phosphate) particles.

[0063] FIG. 8 depicts an assay showing the ability of ILX-5 and ILX-7 to bind to different size hydroxyapatite and bTCP particles.

[0064] FIG. 9 depicts expression level of plasmids encoding ILX-5, ILX-51, and ILX-71 from transformed E. coli THX01.

[0065] FIG. 10 depicts the results of solubility testing for ILX-51 and ILX-71 at various pH levels.

[0066] FIG. 11 depicts the results of solubility testing for ILX-51 and ILX-71 at various Urea concentrations.

[0067] FIG. 12 depicts the results of solubility testing for ILX-71 in a 6M Urea solution versus a 6M GuHCL solutions.

[0068] FIG. 13 depicts the results of assessing the ability of ILX-71 to refold.

[0069] FIG. 14 shows the expression level of ILX-52 from and E. coli induction. FIG. 15 depicts the results of inclusion body solubilization testing for ILX-52 at various Urea concentrations.

[0070] FIG. 16A shows the quantification of the amount of solubilized ILX-52 recovered from an inclusion body using an 8 M Urea buffer. FIG. 16B shows the calibration curve used to calculate the mass of ILX-52 recovered.

[0071] FIG. 17 shows the results of testing the ability of ILX-52 to refold after exposure to an 8M Urea in various concentrations of Urea buffer and a 0.8 M ArgHCL buffer.

[0072] FIG. 18 shows the result of dialyzing the refolded ILX-52 against a dialysis buffer after oxidization with glutathione disulfide.

[0073] FIG. 19 depicts the response of CTLL-2 cells, which respond to IL2 activity, to increasing doses of ILX-5 refolded and dialyzed at various concentrations of Urea versus a control. Proliferation of the CTLL-2 cells was assessed using AlamarBlue reagent.

[0074] FIG. 20 depicts the response of CTLL-2 cells, which respond to IL2 activity, to increasing doses of refolded ILX-5, either free or attached to hydroxyapatite particles or attached to bTCP particles of two different sizes versus a control. Proliferation of the CTLL-2 cells was assessed using AlamarBlue reagent.

[0075] FIG. 21 depicts the expression of multiple HLA constructs (HLA-t, HLA-at, HLA-b) in recombinant E. coli.

[0076] FIG. 22 shows the solubilization of HLA-t from an inclusion body at various concentration of Urea buffer.

[0077] FIG. 23 depicts the expression of the HLA-bat construct in recombinant E. coli.

[0078] FIG. 24A shows the quantification of the amount of solubilized HLA-bat recovered from an inclusion body using an 8 M Urea buffer. FIG. 24B shows the calibration curve used to calculate the mass of HLA-bat recovered.

[0079] FIG. 25 shows the results of refolding HLA-bat with or without TLTSCNTSV peptide after dialyzation against PBS overnight.

[0080] FIG. 26 depicts the expression of the a and b chains for the DR1 MHC-II transformed E. coli THXH01, which shows no significant expression of the DR1 alpha chain.

[0081] FIG. 27A shows the results of administering ILX-52 and a beta-TCP particle (ILX-52 / bTCP) in combination with an anti-PD-1 antibody (lx or 5x anti-PD-1 antibody: ILX-52 / bTCP lx + anti- PD1 or ILX-52 / bTCP + anti-PDl 5x, respectively), as compared to administering the beta-TCP particle (bTCP) or the bTCP and anti-PD-1 antibody, on tumor volumes in a murine melanoma model. The results show an improvement in tumor volume reduction with treatment of ILX-52 / bTCP and anti-PD-1 antibody as compared to treatment with bTCP or treatment with bTCP and anti-PD-1 antibody.

[0082] FIG. 27B shows the results of adminsistering ILX-52 and a beta-TCP particle (ILX-52 / bTCP) in combination with an anti-PD-1 antibody (lx or 5x anti-PD-1 antibody: ILX-52 / bTCP lx + anti- PD1 or ILX-52 / bTCP + anti-PDl 5x, respectively), as compared to administering the beta-TCP particle (bTCP) or the bTCP and anti-PD-1 antibody, on probability of survival in a murine melanoma model. The results show that mice treated with ILX-52 / bTCP and anti-PD-1 antibody 5x survive longer than control.

[0083] FIG. 28A shows the results of adminsistering ILX-52 with betaTCP (ILX-52) or ILX-74 with bTCP (ILX-74) in combination with an anti-PD-1 antibody on tumor volumes in a murine melanoma model, as compared to treatment with bTCP alone. The results show an improvement in tumor reduction volume with treatment of ILX-52 with bTCP and anti-PD-1 antibody as compared to treatment with bTCP. The results show an improvement in tumor reduction volume with treatment of ILX-74 with bTCP and anti-PD-1 antibody as compared to treatment with bTCP.

[0084] FIG. 28B shows the results of adminsistering ILX-52 with betaTCP (ILX-52) or ILX-74 with bTCP (ILX-74) in combination with an anti-PD-1 antibody on probability of survival in a murine melanoma model, as compared to treatment with bTCP alone. The results show that mice treated with ILX-52 with bTCP, and anti-PD-1 antibody survive longer than mice treated with bTCP. The results show that mice treated with ILX-74 with bTCP, and anti-PD-1 antibody survive longer than mice treated with bTCP.

[0085] DETAILED DESCRIPTION

[0086] In various aspects, provided herein are methods of activating an immune response in a subject in need thereof, the methods comprising delivering to the subject an immunomodulatory polypeptide tethered to a delivery particle, wherein the immunomodulatory polypeptide comprises a binding peptide that binds the immunomodulatory polypeptide to the delivery particle. In various aspects, provided herein are methods of treating cancer in a subject in need thereof, the methods comprising delivering to the subject an immunomodulatory polypeptide tethered to a delivery particle, wherein the immunomodulatory polypeptide comprises a binding peptide that binds the immunomodulatory polypeptide to the delivery particle. In some embodiments, the immunomodulatory polypeptide is localized to a target site in the subject. In some embodiments, the immunomodulatory polypeptide tethered to the delivery particle does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the immunomodulatory polypeptide not tethered to the delivery particle. The methods may further comprise delivering to the subject an antigen associated with a cancer of the subject (tumor antigen). The methods may comprise administering to the subject an immune checkpoint inhibitor. As a non-limiting example, an anti-PD-1 antibody.

[0087] Also provided herein are methods of activating an immune response in a subject in need thereof to treat cancer, the methods comprising delivering to the subject an anti -cancer agent bound to a particle comprising a calcium compound. Also provided herein are methods of treating cancer in a subject in need thereof, the methods comprising delivering to the subject an anti -cancer agent bound to a particle comprising a calcium compound. In some embodiments, the methods localize the anticancer agent to a target site in the subject. In some embodiments, the anti -cancer agent does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the anti -cancer agent not tethered to the delivery particle. In some embodiments, the method results in immune activation that is specific for the cancer. In some embodiments, the anti-cancer agent comprises a binding peptide that binds to the calcium compound of the particle. In some embodiments, the anti -cancer agent comprises a protease cleavage site, optionally wherein the protease cleavage site is cleaved by a protease of a T cell and / or a protease of a cancer cell in the subject. The methods may further comprise delivering to the subject an antigen associated with the cancer of the subject (tumor antigen). The methods may comprise administering to the subject an immune checkpoint inhibitor. As a non -limiting example, an anti-PD-1 antibody.

[0088] Also provided herein are compositions and systems for modulating an immune response in a subject. The compositions and systems may be used in the methods described herein. An example composition comprises a peptide fusion protein. In various embodiments, provided is a peptide fusion protein comprising a binding peptide connected to an immunomodulatory polypeptide, wherein the binding peptide interacts with a delivery particle to tether the peptide fusion to the delivery particle. In some embodiments, the binding peptide binds to the delivery particle. In some embodiments, the delivery particle comprises a calcium compound, and the binding peptide binds to the calcium compound. Non-limiting example immunomodulatory peptides include interleukins (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF-related apoptosis-inducing ligand (TRAIL), and Interleukin 4 (IL4).

[0089] In various embodiments herein, the immunomodulatory polypeptide comprises an interleukin. In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 15-16.

[0090] In various embodiments herein, the immunomodulatory polypeptide comprises a human leukocyte antigen (HLA) receptor. In some embodiments, the HLA receptor comprises the alpha chain of the HLA receptor and / or the beta chain of the HLA receptor. In some embodiments, the HLA receptor is a Class I or a Class II HLA receptor. In some embodiments, the HLA receptor comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 17-22, 53, 122.

[0091] In various embodiments herein, provided are compositions, systems, and kits comprising an immunomodulatory polypeptide and / or anti -cancer agent, and a delivery particle. In some embodiments, the delivery particle comprises a calcium compound. Non-limiting example calcium compounds include calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, hydroxyapatite, a metal oxide, or an oxygen or nitrogen passivated material. In various embodiments herein, provided are compositions, systems, and kits comprising an immunomodulatory polypeptide and / or anti -cancer agent, optionally a delivery particle, and a tumor antigen peptide. In some embodiments, the tumor antigen peptide is specific to a cancer from the subject.

[0092] Also provided herein are nucleic acids encoding polypeptides and peptide fusion proteins herein. Further provided are vectors comprising the nucleic acids.

[0093] Binding Peptides

[0094] In one aspect, provided herein are binding peptides. The binding peptides may bind to a particle or component thereof. In some embodiments, the binding peptides bind to a calcium compound of a particle. Non-limiting example binding peptides are provided in Table 1.

[0095] In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, a binding peptide comprises a sequence at least

[0096] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0097] 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,

[0098] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0099] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0100] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0101] ID NO: 5. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%,

[0102] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, a binding peptide comprises a sequence at least

[0103] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0104] 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,

[0105] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0106] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0107] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0108] ID NO: 10. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%,

[0109] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, a binding peptide comprises a sequence at least

[0110] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0111] 97%, 98%, or 99% identical to SEQ ID NO: 12. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, a binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0112] ID NO: 6. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0113] 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0114] 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0115] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0116] ID NO: 12. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0117] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%,

[0118] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14.

[0119] Table 1. Non-limiting example binding peptides.

[0120] Therapeutic Agents

[0121] In one aspect, provided herein are therapeutic agents. Non -limiting example therapeutic agents include immunomodulatory agents, anti -cancer agents, and antigen peptides. Sequences for non-limiting example peptide therapeutic agents are provided in Table 2.

[0122] Various embodiments include an immunomodulatory agent as a therapeutic agent. In some embodiments, the immunomodulatory agent is an immunomodulatory peptide. Non-limiting example immunomodulatory peptides include interleukins (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF -related apoptosisinducing ligand (TRAIL), and Interleukin 4 (IL4). In example embodiments, the immunomodulatory peptide comprises an interleukin. For instance, the interleukin is IL-2, IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In example embodiments, the immunomodulatory peptide comprises a human leukocyte antigen (HLA) receptor. The HLA receptor may be a Class I receptor. For instance, an HLA-A, HLA-B, or HLA-C. The HLA receptor may be a Class II receptor. The HLA receptor may have an alpha chain and a beta chain, which may be present on a single, or two separate peptide molecules.

[0123] Various embodiments include an anti -cancer agent as a therapeutic agent. In some embodiments, the anti -cancer agent comprises interleukins (IL), Interferon alfa (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF-related apoptosis-inducing ligand (TRAIL), or Interleukin 4 (IL4). In example embodiments, the anti -cancer agent comprises an interleukin. For instance, the interleukin is IL-2, IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In example embodiments, the anti -cancer agent comprises a human leukocyte antigen (HLA) receptor. The HLA receptor may be a Class I receptor. For instance, an HLA-A, HLA-B, or HLA-C. The HLA receptor may be a Class II receptor. The HLA receptor may have an alpha chain and a beta chain, which may be present on a single, or two separate peptide molecules. If the HLA receptor comprises an alpha and a beta chain, the peptide may also include a connecting peptide positioned between the alpha chain and the beta chain. Non-limiting example connecting peptides include linker peptides of Table 4, and peptides at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to peptides of Table 4.

[0124] Various embodiments include an antigen peptide as a therapeutic agent. The antigen peptide may be present on a cancer cell. The antigen peptide may be at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to an antigen of a cancer cell. The antigen may comprise any one of the sequences in Table 5. The antigen peptide may be at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0125] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence in Table 5. The antigen may comprise any one of SEQ ID NOS: 58-93. The antigen peptide may be at least 80%, 81%, 82%, 83%,

[0126] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of any one of SEQ ID NOS: 58-93.

[0127] In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anticancer agent, comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 17. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti-cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0128] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti-cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0129] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 20. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti-cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0130] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 21. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti-cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0131] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 22. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0132] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 23. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0133] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 122. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0134] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 53. In some embodiments, atherapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0135] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 94. In some embodiments, atherapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0136] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 95. In some embodiments, atherapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0137] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 96. In some embodiments, atherapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0138] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 97. In some embodiments, atherapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0139] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 98. In some embodiments, atherapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%,

[0140] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 99. In some embodiments, a therapeutic agent, such as an immunomodulatory agent and / or anti -cancer agent, comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 100.

[0141] In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 17. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 20. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 21. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 22. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0142] ID NO: 23. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 122. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0143] 98%, or 99% identical to SEQ ID NO: 53. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 94. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 95. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 96. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 97. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 98. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 99. In some embodiments, a polypeptide, fusion protein, composition, system, or kit herein comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 100.

[0144] Table 2. Non-limiting example therapeutic agents.

[0145] Table 5. Non-limiting examples of neoantigens

[0146] Polypeptides, Fusion Proteins, Metabolites and Compositions

[0147] In one aspect, provided herein are polypeptides comprising a binding peptide (e.g., a peptide capable of binding to a carrier material) and a therapeutic agent. In certain embodiments, the polypeptides are fusion proteins. Also provided herein are compositions comprising polypeptides and fusion proteins herein. Non-limiting example binding peptides include those of Table 1, and peptides having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 1. Non-limiting example therapeutic agents include immunomodulatory agents, anti -cancer agents, antigen peptides, peptides of Table 2, and peptides having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 2. In some embodiments, the binding peptide and therapeutic agent are connected via a linker. Non-limiting example linkers include peptides of Table 4, and peptides having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 4. If present, the linker may comprise a protease cleavage site. Non-limiting example peptides and fusion proteins are provided in Table 3. Each of the sequences in Table 3 may include an N-terminal methionine for recombinant protein expression.

[0148] Non-limiting configurations of fusion proteins provided herein include:

[0149] TA - BP (Formula 1),

[0150] TA - L - BP (Formula 2),

[0151] BP - TA (Formula 3),

[0152] BP - L - TA (Formula 4),

[0153] TAI - LI - BP - L2 - TA2 (Formula 5), TAI - BP - TA2 (Formula 6),

[0154] TAI - LI - BP - TA2 (Formula 7),

[0155] TAI - BP - LI - TA2 (Formula 8)

[0156] BP1 - LI - TA - L2 - BP2 (Formula 9),

[0157] BP 1 - TA - BP2 (Formula 10),

[0158] BP1 - LI - TA - BP2 (Formula 11), and

[0159] BP1 - TA - LI - BP2 (Formula 12), wherein each TA is a therapeutic agent, each L is a linker, and each BP is a binding peptide. The linker may comprise any linker herein, and may include a protease cleavage site. If a formula includes TAI and TA2, in some cases the TAI and TA2 are the same, and in some cases the TAI and TA2 are different. If a formula includes LI and L2, in some cases the LI and L2 are the same, and in some cases the LI and L2 are different. If a formula includes BP1 and BP2, in some cases the BP1 and BP2 are the same, and in some cases the BP1 and BP2 are different. In some formulas, the BP represents one or more binding peptides, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 binding peptides, which can include the same, or two or more different binding peptides. In some cases, the TA comprises an immunomodulatory agent. In some cases, the TA comprises an anti -cancer agent. In some cases, the TA comprises a first TA and a second TA, optionally connected via a connecting peptide or linker.

[0160] In some embodiments, each therapeutic agent (e.g., TA, TAI, and TA2) independently comprises: an immunomodulatory agent, an anti -cancer agent, an antigen peptide, or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 15-23, 53, 58-100, and 122. In some embodiments, the therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16.

[0161] In some embodiments, each linker (e.g., L, LI, and L2) independently comprises a (i) furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, (v) one or more of SEQ ID NOS: 36-52, 124-125, 127-128, and 101-113, or

[0162] (vi) any combination of (i) to (v). In some embodiments, the linker comprises a sequence at least

[0163] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0164] 97%, 98%, or 99% identical to SEQ ID NO: 42 and / or a sequence at least 80%, 81%, 82%, 83%,

[0165] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111 . In some embodiments, the linker comprises a sequence at least 80%,

[0166] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0167] 98%, or 99% identical to SEQ ID NO: 43, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0168] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0169] NO: 103, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0170] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0171] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0172] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103, a sequence at least 80%, 81%,

[0173] 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0174] 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109. In some embodiments, the linker comprises one or more of SEQ ID NOS: 36-52, 124-125, and 101-113. In some embodiments, the linker comprises a protease cleavage site, e.g., a furin cleavage site, a caspase cleavage site, a matrix metalloproteinase cleavage site, a cathepsin cleavage site, or a combination of cleavage sites. In some embodiments, the linker comprises a furin cleavage site.

[0175] In some embodiments, each binding peptide (e.g., BP, BP1, and BP2) is independently a binding peptide, and each binding peptide independently comprises a sequence at least 80%, 81%,

[0176] 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0177] 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0178] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0179] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0180] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0181] ID NO: 14.

[0182] In some embodiments, the formulas for the fusion proteins are not limiting, and as such, may include one or more additional sequences. For example, provided are fusion proteins having Formula 1, wherein an additional peptide is positioned between TA and BP, prior to TA, or after BP, or any combination thereof.

[0183] In some embodiments of a fusion protein, polypeptide, or composition herein, the fusion protein, polypeptide, or composition comprises a protease cleavage site, wherein cleavage by a protease generates a metabolite. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0184] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 115. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0185] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 116.

[0186] In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%,

[0187] 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0188] 99% identical to SEQ ID NO: 117. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 118. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 119. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 120. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 121. In some embodiments, provided herein is a metabolite comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 126.

[0189] Table 3. Non-limiting example fusion proteins and metabolites.

[0190] In some embodiments, polypeptides and fusion proteins described herein comprise two or more binding peptides (e.g., BP, BP1, BP2, etc). In some embodiments, the two or more binding peptides is about 2, 3, 4, 5, 6, 7, 8, 9, or 10 binding peptides. In some embodiments, each binding peptide is about 5 to about 15 amino acids, about 10 to about 15 amino acids, or about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids. In some embodiments, the total number of amino acids within two or more binding peptides is about 10 to about 100, about 10 to about 90, about 10 to about 80, about

[0191] 10 to about 70, about 10 to about 60, about 10 to about 50, about 10 to about 40, about 10 to about 30, about 20 to about 100, about 20 to about 90, about 20 to about 80, about 20 to about 70, about 20 to about 60, about 20 to about 50, about 20 to about 40, or about 30 to about 80 amino acids.

[0192] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0193] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15.

[0194] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0195] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0196] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0197] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0198] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0199] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0200] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0201] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0202] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0203] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0204] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0205] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0206] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0207] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0208] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0209] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0210] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0211] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0212] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0213] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0214] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0215] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0216] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0217] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0218] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0219] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0220] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0221] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0222] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0223] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0224] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0225] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0226] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0227] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0228] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0229] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0230] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 17.

[0231] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0232] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0233] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0234] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0235] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0236] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0237] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0238] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0239] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0240] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0241] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0242] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0243] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0244] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0245] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0246] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0247] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0248] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0249] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0250] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0251] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0252] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0253] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0254] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0255] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0256] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0257] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0258] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0259] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0260] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0261] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0262] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0263] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0264] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0265] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0266] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0267] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0268] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0269] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0270] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0271] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0272] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0273] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0274] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0275] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0276] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0277] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0278] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0279] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0280] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0281] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0282] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0283] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0284] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0285] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 20. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0286] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0287] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0288] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0289] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0290] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0291] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0292] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0293] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0294] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0295] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0296] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0297] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0298] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0299] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0300] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0301] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0302] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0303] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 21 . In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%. 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0304] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0305] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0306] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0307] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0308] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0309] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0310] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0311] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0312] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0313] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0314] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0315] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0316] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0317] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0318] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0319] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound. In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0320] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 22.

[0321] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0322] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0323] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0324] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0325] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0326] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0327] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0328] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0329] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0330] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0331] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0332] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0333] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0334] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0335] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0336] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0337] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0338] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0339] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0340] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 122. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0341] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0342] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0343] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0344] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0345] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0346] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0347] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0348] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0349] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0350] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0351] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0352] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0353] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0354] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0355] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0356] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0357] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0358] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 53. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0359] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0360] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0361] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0362] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0363] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0364] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0365] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0366] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0367] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0368] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0369] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0370] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0371] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0372] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0373] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0374] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0375] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 94. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0376] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0377] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0378] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0379] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0380] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0381] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0382] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0383] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0384] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0385] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0386] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0387] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0388] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0389] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0390] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0391] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0392] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0393] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 95.

[0394] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0395] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0396] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0397] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0398] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0399] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0400] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0401] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0402] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0403] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0404] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0405] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0406] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0407] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0408] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0409] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0410] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0411] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 96. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0412] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0413] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0414] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0415] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0416] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0417] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0418] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0419] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0420] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0421] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0422] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0423] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0424] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0425] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0426] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0427] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0428] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0429] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 97. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0430] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0431] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0432] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0433] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0434] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0435] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0436] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0437] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%. 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0438] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0439] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0440] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0441] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0442] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0443] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0444] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0445] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0446] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 98.

[0447] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0448] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0449] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0450] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0451] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0452] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0453] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0454] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0455] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0456] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0457] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0458] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0459] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0460] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0461] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0462] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0463] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0464] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0465] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0466] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 99. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0467] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0468] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0469] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0470] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0471] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0472] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0473] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0474] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0475] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0476] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0477] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0478] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0479] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0480] In some embodiments, provided herein is a polypeptide or fusion protein comprising a first binding peptide (e.g., BP, BP1, BP2, etc.) and a first therapeutic agent (e.g., TA, TAI, TA2, etc.), the first therapeutic agent comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0481] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 100.

[0482] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0483] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0484] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0485] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0486] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0487] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0488] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0489] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0490] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0491] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0492] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0493] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0494] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12.

[0495] In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%,

[0496] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13. In some embodiments, the first binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0497] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14. The polypeptide or fusion protein may comprise two or more additional binding peptides, wherein one or more of the additional binding peptides are optionally selected from a sequence from Table 1, or a sequence at least 80%, 81%, 82%,

[0498] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more sequences of Table 1. The polypeptide or fusion protein may comprise one or more linkers (e.g., L, LI, L2, etc.), e.g., at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0499] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more linkers of

[0500] Table 4. Further provided are compositions, systems, and kits comprising the polypeptide of fusion protein and a particle. The binding peptide may bind to the particle. For example, the particle comprises a calcium compound and the binding peptide binds to the calcium compound.

[0501] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0502] SEQ ID NO: 12 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS), and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT). In some embodiments, the binding peptide and the interleukin -2 are connected via a linker (e.g., L, LI, L2, etc.). In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 (GGGSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGG). In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0503] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0504] NO: 103. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%,

[0505] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0506] SEQ ID NO: 109. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%,

[0507] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the linker comprises a sequence at least 80%,

[0508] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0509] 98%, or 99% identical to SEQ ID NO: 104. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0510] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 36. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0511] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103 and a sequence at least 80%, 81%,

[0512] 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0513] 99% identical to SEQ ID NO: 37. In some embodiments, the linker comprises a sequence at least

[0514] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0515] 97%, 98%, or 99% identical to SEQ ID NO: 103 and a sequence at least 80%, 81%, 82%, 83%, 84%,

[0516] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%,

[0517] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0518] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104.

[0519] In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0520] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0521] ID NO: 109 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0522] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0523] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 50

[0524] (RKKRSTDEVDGAPPLGLWAVGGGG). In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0525] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 112. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0526] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 113. In some embodiments, the linker comprises a furin cleavage site. In some embodiments, the linker comprises a caspase cleavage site. In some embodiments, the linker comprises a matrix metalloprotease (MMP) cleavage site. In some embodiments, the linker comprises a cathepsin cleavage site. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,

[0527] 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0528] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 49.

[0529] In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0530] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0531] ID NO: 106. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%,

[0532] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 107. In some embodiments, the linker comprises a sequence at least 80%,

[0533] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0534] 98%, or 99% identical to SEQ ID NO: 108. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0535] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 127. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,

[0536] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 128. In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,

[0537] 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 24 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSGG

[0538] GSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGGRKKRSTDEVDGAPPLGLWAVGGGG

[0539] APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT). In some embodiments, the polypeptide comprises SEQ ID NO: 24. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13

[0540] (AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAE STSKKRPFS), a first interleukin-2, and a second interleukin-2, wherein each of the first interleukin-2 and the second interleukin-2 independently comprise a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0541] SEQ ID NO: 16

[0542] (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT). In some embodiments, the binding peptide is positioned between the first interleukin-2 and the second interleukin -2. In some embodiments, the binding peptide and the first interleukin -2 are connected via a first linker (e.g., L, LI, L2, etc.). In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 124. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106. In some embodiments, the first linker comprises a sequence at least

[0543] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0544] 97%, 98%, or 99% identical to SEQ ID NO: 109. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,

[0545] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0546] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 36. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0547] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0548] NO: 111. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%,

[0549] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104. In some embodiments, the first linker comprises a furin cleavage site.

[0550] In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0551] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0552] ID NO: 103 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0553] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0554] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0555] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106 and a sequence at least

[0556] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0557] 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,

[0558] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47 and a sequence at least 80%, 81%,

[0559] 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0560] 99% identical to SEQ ID NO: 109. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0561] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47 and a sequence at least 80%, 81%, 82%, 83%,

[0562] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the first linker comprises a sequence at least 80%,

[0563] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0564] 98%, or 99% identical to SEQ ID NO: 109 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0565] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0566] ID NO: 104. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%,

[0567] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0568] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 36.

[0569] In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0570] ID NO: 109 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,

[0571] 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 110. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0572] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0573] NO: 37 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 36. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0574] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 110. In some embodiments, the binding peptide and the second interleukin-2 are connected via a second linker (e.g., L, LI, L2, etc.). In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0575] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0576] NO: 125. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%,

[0577] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103. In some embodiments, the second linker comprises a sequence at least

[0578] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0579] 97%, 98%, or 99% identical to SEQ ID NO: 109. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 36. In some embodiments, the second linker comprises a sequence at least

[0580] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0581] 97%, 98%, or 99% identical to SEQ ID NO: 110. In some embodiments, the second linker comprises a furin cleavage site. In some embodiments, the second linker comprises a sequence at least 80%,

[0582] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0583] 98%, or 99% identical to SEQ ID NO: 103 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0584] ID NO: 37. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%,

[0585] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0586] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109.

[0587] In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%,

[0588] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0589] SEQ ID NO: 37 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 37 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 109 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0590] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0591] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47 and a sequence at least

[0592] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0593] 97%, 98%, or 99% identical to SEQ ID NO: 104. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0594] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47 and a sequence at least 80%, 81%,

[0595] 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0596] 99% identical to SEQ ID NO: 36. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0597] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47 and a sequence at least 80%, 81%, 82%, 83%,

[0598] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 110. In some embodiments, the second linker comprises a sequence at least

[0599] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0600] 97%, 98%, or 99% identical to SEQ ID NO: 106 and a sequence at least 80%, 81%, 82%, 83%, 84%,

[0601] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0602] SEQ ID NO: 104. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or

[0603] 99% identical to SEQ ID NO: 106 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0604] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0605] NO: 36. In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%,

[0606] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 106 and a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0607] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 110.

[0608] In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%,

[0609] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0610] SEQ ID NO: 114

[0611] (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE

[0612] LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS

[0613] IISTLTGGGSGGHMGSGGRKKRSTEAAAKEAAAKEAAAKGGGSGGGSGGAAESTSKKRPFSI

[0614] LAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSGGGS

[0615] GGHMGSGGEAAAKEAAAKEAAAKRKKRSTGGGSGGGSGGAPTSSSTKKTQLQLEHLLLDL QMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPR DLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQSIISTLT). In some embodiments, the polypeptide comprises SEQ ID NO: 114.

[0616] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0617] SEQ ID NO: 12

[0618] (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS), a first interleukin-2, and a second interleukin-2, wherein each of the first interleukin-2 and the second interleukin-2 independently comprise a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16

[0619] (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLT). In some embodiments, the binding peptide is positioned between the first interleukin -2 and the second interleukin -2. In some embodiments, the binding peptide and the first interleukin -2 are connected via a first linker (e.g., L, LI, L2, etc.). In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 46 or 101. In some embodiments, the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 50

[0620] (RKKRSTDEVDGAPPLGLWAVGGGG). In some embodiments, the binding peptide and the second interleukin-2 are connected via a second linker (e.g., L, LI, L2, etc.). In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 (GGGSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGG). In some embodiments, the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 50 (RKKRSTDEVDGAPPLGLWAVGGGG). In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 25

[0621] (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLTRKKRSTDEVDGAPPLGLWAVGGGGSGGGSGGEAAAKEAAAKEAAAKGGGSGGHM

[0622] GSGGAAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPW

[0623] TAAESTSKKRPFSGGGSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGGRKKRSTDEVD

[0624] GAPPLGLWAVGGGGAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMP KKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADE TATIVEFLNRWITFSQSIISTLT). In some embodiments, the polypeptide comprises SEQ ID NO: 25.

[0625] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0626] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0627] SEQ ID NO: 11, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0628] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0629] SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTAS GAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGAPTSSSTKKTQLQLEHLLLDLQMILN GINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNI NVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT).

[0630] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0631] SEQ ID NO: 11, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0632] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0633] SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 27 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTAS GAGGSGGGGSGGGTSGATGAGTSTSGGGASTGGGTGAPTSSSTKKTQLQLEHLLLDLQMILN

[0634] GINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNI NVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT).

[0635] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0636] SEQ ID NO: 11, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0637] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0638] SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 28 (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTAS GAGGSKGGGSKGGTSGATGAGTSTSGGGASTGGGTGAPTSSSTKKTQLQLEHLLLDLQMILN GINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNI NVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT).

[0639] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0640] SEQ ID NO: 12, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0641] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0642] SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 29 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSGG GSGGHKGGGGKEAAAKEAAAKEAAAKGGGGSGGGGAPTSSSTKKTQLQLEHLLLDLQMIL NGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT).

[0643] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0644] SEQ ID NO: 12, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0645] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0646] SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0647] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 30 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSGG GSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGGAPTSSSTKKTQLQLEHLLLDLQMIL NGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT). In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 31 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQ SIISTLTASGAGGSEGGGSEGGTSGATGAGTSTSGGGASTGGGTGLLADTTHHRPWTVIGEST HHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTASGAGGSEGGGSEGGTSGAT GAGTSTSGGGASTGGGTGAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKF YMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEY ADETATIVEFLNRWITFCQSIISTLT). In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 32 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQ SIISTLTGGGSGGHKGGGGKEAAAKEAAAKEAAAKGGGGSGGGGILAETTHHRPWSSTADT SHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSASGAGGSKGGGSKGGTSGA TGAGTSTSGGGASTGGGTGAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFK FYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCE YADETATIVEFLNRWITFCQSIISTLT). In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0648] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0649] SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%,

[0650] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%,

[0651] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0652] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0653] NO: 33

[0654] (LLADTTHHRPWTVIGESTHHRPWSIIGESSHHKPFTGLGDTTHHRPWGILAESTHHKPWTGG

[0655] GSGGHKGGGGKEAAAKEAAAKEAAAKGGGGSGGGGAPTSSSTKKTQLQLEHLLLDLQMIL

[0656] NGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS

[0657] NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLTGGGSGGHMGSGGEAAAKE

[0658] AAAKEAAAKGGGSGGGSGGILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTH

[0659] HSPWTAAESTSKKRPFS) .

[0660] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0661] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0662] SEQ ID NO: 12, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0663] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0664] SEQ ID NO: 16. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSGG GSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGGAPTSSSTKKTQLQLEHLLLDLQMIL NGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLIS NINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQSIISTLT).

[0665] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide (e.g., BP, BP1, BP2, etc.) comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0666] SEQ ID NO: 12, and an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%,

[0667] 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to

[0668] SEQ ID NO: 16. In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0669] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 35 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEE LKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFSQS IISTLTGGGSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGGAAESTSKKRPFSILAETTH HRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFSGGGSGGHMG SGGEAAAKEAAAKEAAAKGGGSGGGSGGAPTS S STKKTQLQLEHLLLDLQMILNGINNYKN PKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLEL KGSETTFMCEYADETATIVEFLNRWITFSQSIISTLT).

[0670] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS), and an HLA receptor comprising (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 17 (GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWD GETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETL QRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWE), and (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 18 (IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY LLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM). In some embodiments, (i) and (ii) are connected via a connecting peptide. In some embodiments, the connecting peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 45 (GGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSG G). In some embodiments, the connecting peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 52 (GSSSSGSSSSGSSSS). In some embodiments, the HLA receptor comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 19 (GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWD GETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETL QRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWE GGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSG GMIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWS FYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM). In some embodiments, the HLA receptor comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 53 (IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY LLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM GSSSSGSSSSGSSSS GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDG ETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGK DYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTF QKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWE). In some embodiments, the binding peptide and the HLA receptor are connected via a linker. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 (GGGSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGG). In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43 or 102. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 50 (RKKRSTDEVDGAPPLGLWAVGGGG). In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 54

[0671] (GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWD GETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETL QRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEGGSGGGGSGGGGSGGGGSGGGGSG GGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGMIQRTPKIQVYSRHPAENGKSNFLN CYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTL SQPKIVKWDRDM GGGSGGHMGSGGEAAAKEAAAKEAAAKGGGSGGGSGGILAETTHHRPWSSTADTSHHRPS TVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS). In some embodiments, the polypeptide comprises SEQ ID NO: 54. In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55

[0672] (IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY LLYYTEFTPTEKDEYACRVNHVTLS QPKIVKWDRDMGS SSSGSSSSGSSS SGSHSMRYFFTS V SRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQT HRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRS WTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMT HHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPS GQEQRYTCHVQHEGLPKPLTLRWERKKRSTDEVDGAPPLGLWAVGGGGEAAAKEAAAKEA AAKGGGSGGGSGGLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLI ADSTHHSPWTLIADSTHHSPWT). In some embodiments, the polypeptide comprises SEQ ID NO: 55.

[0673] In some embodiments, provided herein is a polypeptide or fusion protein comprising a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14 (LIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIA DSTHHSPWT), and an HLA receptor comprising (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 22 (GDTRPRFLWQLKFECHFFNGTERVRLLERSIYNQEESVRFDSDVGEYRAVTELGRPDAEYW NSQKDLLEQRRAAVDTYCRHNYGVGESFTVQRRVEPKVTVYPSKTQPLQHHNLLVCSVSGF YPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPL TVEWRA). In some embodiments, the binding peptide and the HLA receptor are connected via a linker. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43 or 102. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 50 (RKKRSTDEVDGAPPLGLWAVGGGG). In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 56 (GDTRPRFLWQLKFECHFFNGTERVRLLERSIYNQEESVRFDSDVGEYRAVTELGRPDAEYW NSQKDLLEQRRAAVDTYCRHNYGVGESFTVQRRVEPKVTVYPSKTQPLQHHNLLVCSVSGF YPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPL TVEWRARKKRSTDEVDGAPPLGLWAVGGGGEAAAKEAAAKEAAAKGGGSGGGSGGLIAD STHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHH SPWT). In some embodiments, the polypeptide comprises SEQ ID NO: 56. In some embodiments, the polypeptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 57 (IKEEHVIIQAEFYLNPDQSGEFMFDFDGDEIFHVDMAKKETVWRLEEFGRFASFEAQGALAN IAVDKANLEIMTKRSNYTPITNVPPEVTVLTNSPVELREPNVLICFIDKFTPPVVNVTWLRNGK PVTTGVSETVFLPREDHLFRKFHYLPFLPSTEDVYDCRVEHWGLDEPLLKHWEFDAPSPLPET

[0674] TERKKRSTDEVDGAPPLGLWAVGGGGEAAAKEAAAKEAAAKGGGSGGGSGGLIADSTHHS

[0675] PWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWT). In some embodiments, the polypeptide comprises SEQ ID NO: 57.

[0676] Linkers

[0677] In some aspects, polypeptides, fusion proteins, and compositions herein comprise a linker. The linker may be positioned between a binding peptide and a therapeutic agent. The linker may be positioned between a first therapeutic agent and a second therapeutic agent.

[0678] In some embodiments, the linker comprises a flexible linker, where at least about four of the amino acids have no regular secondary structure. In some embodiments, regular secondary structure comprises any helical structure (e.g., an alpha helix, 3 io helix, n helix), a beta turn, omega loop, and / or a beta sheet. In some embodiments, the flexible linker is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% or 90% glycine, serine, or glycine and serine residues. In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having GGGS (SEQ ID NO: 36). In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having GGSGG (SEQ ID NO: 44). In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having SEQ ID NO: 45. In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having SEQ ID NO: 52. In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having SEQ ID NO: 104. In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having SEQ ID NO: 110. In some embodiments, the linker comprises 1, 2, 3, 4, or 5 sequences having SEQ ID NO: 111.

[0679] In some embodiments, the linker comprises a rigid linker, where at least seven of the amino acids form a helical structure. In some embodiments, the rigid linker comprises 1, 2, 3, 4, or 5 sequences having (EAAAK)n (SEQ ID NO: 37), where n is 1 to 5. In some cases, n is 1. In some cases, n is 2. In some cases, n is 3. In some cases, n is 4. In some cases, n is 5. In some cases, the linker comprises SEQ ID NO: 109. In some embodiments, the linker comprises a flexible and a rigid linker.

[0680] In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 38. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 39. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 40. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 41. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

[0681] 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,

[0682] 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 46. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,

[0683] 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 51.

[0684] In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0685] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0686] ID NO: 101. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%,

[0687] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 102. In some embodiments, the linker comprises a sequence at least 80%,

[0688] 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,

[0689] 98%, or 99% identical to SEQ ID NO: 103. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0690] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 124. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 125.

[0691] In some embodiments, the linker comprises a protease cleavage site. The cleavage site may be cleaved by a protease present in the microenvironment of a cancer. The cleavage site may be cleaved by a protease of an immune cell. Example cleavage sites include those cleaved by furin, caspase, cathepsin, and matrix metalloprotease (MMP). Example furin cleavage sites include SEQ ID NO: 47 and SEQ ID NO: 106. Example caspase cleavage sites include SEQ ID NO: 48 and SEQ ID NO: 107. Example MMP cleavage sites include SEQ ID NO: 49 and SEQ ID NO: 108. Example cathepsin cleavage sites include SEQ ID NO: 127 and SEQ ID NO: 128. In some embodiments, the linker comprises 1, 2, 3, 4 or 5 protease cleavage sites. Non-limiting example cleavage sites include those having SEQ ID NOS: 47-50, and peptides at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to peptides having SEQ ID NOS: 47-50. Non-limiting example cleavage sites include those having SEQ ID NOS: 106-108, and peptides at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to peptides having SEQ ID NOS: 106-108. Nonlimiting example cleavage sites include those having SEQ ID NOS: 112-113, and peptides at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0692] 97%, 98%, or 99% identical to peptides having SEQ ID NOS: 112-113. Non-limiting example cleavage sites include those having SEQ ID NOS: 124-125, and peptides at least 80%, 81%, 82%,

[0693] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to peptides having SEQ ID NOS: 124-125. Non-limiting example cleavage sites include those having SEQ ID NOS: 127-128, and peptides at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to peptides having SEQ ID NOS: 127-128. In some embodiments, the linker comprises a sequence of about 5 to about 50 amino acids.

[0694] For example, a sequence of about 5 to about 45, about 5 to about 40, about 5 to about 35, about 5 to about 30, about 5 to about 20, about 5 to about 15, about 10 to about 50, about 10 to about 45, about 10 to about 40, about 10 to about 35, about 10 to about 30, about 10 to about 25, about 10 to about 20, about 10 to about 15, about 15 to about 50, about 15 to about 45, about 15 to about 40, about 15 to about 35, about 15 to about 30, about 15 to about 25, about 15 to about 20, about 20 to about 50, about 20 to about 45, about 20 to about 40, about 20 to about 35, about 20 to about 30, about 20 to about 25, about 25 to about 50, about 25 to about 45, about 25 to about 40, about 25 to about 35, about 25 to about 30, about 30 to about 50, about 30 to about 45, about 30 to about 40, about 30 to about 35, about 35 to about 50, about 35 to about 45, about 35 to about 40, about 40 to about 50, about 40 to about 45, about 45 to about 50, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 amino acids.

[0695] Table 4. Non-limiting example linkers, protease cleavage sites, and linkers comprising protease cleavage sites.

[0696] Nucleic Acids / Vectors

[0697] Also provided herein are nucleic acids that encode any of the peptides, polypeptides, fusion proteins, and compositions described herein.

[0698] Also provided herein are vectors that include any of the nucleic acids provided herein. The vector may refer to a polynucleotide capable of inducing the expression of a recombinant peptide in a host cell. In some embodiments, the vector further comprises a promoter and / or enhancer operably linked to any of the nucleic acids described herein.

[0699] Methods of Production

[0700] Also provided herein are methods of making any of the peptides, polypeptides, fusion proteins, and compositions, which includes introducing into a cell a nucleic acid sequence encoding the peptide to produce a recombinant cell; and culturing the recombinant cell under conditions sufficient for the expression of the peptide. In some embodiments, the introducing step includes introducing into a cell an expression vector including a nucleic acid sequence encoding the peptide.

[0701] Provided herein are methods that include isolation of the peptide from a cell, e.g., ionexchange chromatography, affinity chromatography, and / or size exclusion chromatography.

[0702] Carrier Materials

[0703] In one aspect, provided herein are carrier materials (sometimes referred to as carrier particles, delivery particles, delivery materials, or particles) that may be combined with a polypeptide, binding peptide, therapeutic agent, fusion protein, and / or other composition described herein. In some embodiments, a binding peptide binds to the carrier material. In some embodiments, a carrier material is a material for which a binding peptide herein is capable of binding.

[0704] In some embodiments, the carrier material comprises a calcium compound. Non-limiting example calcium compounds include calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, hydroxyapatite, a metal oxide, or an oxygen or nitrogen passivated material. In some embodiments, the calcium compound comprises calcium phosphate. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate.

[0705] In certain non-limiting embodiments, beta-tricalcium phosphate is referred to alternatively as beta-tricalcium phosphate, beta-TCP, b-TCP, bTCP, P-TCP, and / or P-TCP.

[0706] In some embodiments, the carrier material is a particle having a diameter of about 1 micron to about 150 microns. In some embodiments, the carrier material is a particle having a diameter of about 5 microns to about 50 microns. In some embodiments, the carrier material is a particle having a diameter of about 40 microns. In some embodiments, the carrier material is a particle having a diameter of at least 1 micron, at least 5 microns, at least 10 microns, at least 15 microns, at least 20 microns, at least 25 microns, at least 30 microns, at least 35 microns, at least 40 microns, at least 45 microns, at least 50 microns, at least 55 microns, at least 60 microns, at least 65 microns, at least 70 microns, at least 75 microns, at least 80 microns, at least 85 microns, at least 90 microns, at least 95 microns, at least 100 microns, at least 105 microns, at least 110 microns, at least 115 microns, at least 120 microns, at least 125 microns, at least 130 microns, at least 135 microns, at least 140 microns, at least 145 microns, at least 150 microns, at least 160 microns, at least 170 microns, at least 180 microns, at least 190 microns, at least 200 microns, or more.

[0707] In some embodiments, the carrier material is a particle having a diameter of no larger than 1 micron, no larger than 5 microns, no larger than 10 microns, no larger than 15 microns, no larger than 20 microns, no larger than 25 microns, no larger than 30 microns, no larger than 35 microns, no larger than 40 microns, no larger than 45 microns, no larger than 50 microns, no larger than 55 microns, no larger than 60 microns, no larger than 65 microns, no larger than 70 microns, no larger than 75 microns, no larger than 80 microns, no larger than 85 microns, no larger than 90 microns, no larger than 95 microns, no larger than 100 microns, no larger than 105 microns, no larger than 110 microns, no larger than 115 microns, no larger than 120 microns, no larger than 125 microns, no larger than 130 microns, no larger than 135 microns, no larger than 140 microns, no larger than 145 microns, no larger than 150 microns, no largerthan 160 microns, no larger than 170 microns, no larger than 180 microns, no largerthan 190 microns, no larger than 200 microns, or more. In some embodiments, the carrier material may be a particle having a diameter in a range defined by any of the previous values. Compositions and Kits

[0708] Also provided herein are compositions (e.g., pharmaceutical compositions) that include any of the binding peptides, polypeptides, therapeutic agents, and / or fusion proteins described herein. In some examples, the compositions and kits further include a carrier material provided herein. In some embodiments, the compositions are bound to the carrier material.

[0709] In some instances, the compositions are disposed in a sterile vial or a pre-loaded syringe.

[0710] In some instances, the compositions are formulated for different routes of administration. Non-limiting examples include via intratumoral (IT) injection, guided injection to a lymph node, subcutaneous, intramuscular, or tumor embolization via venous catheter. Also provided herein are kits that include any of the compositions, binding peptides, polypeptides, therapeutic agents, and / or fusion proteins described herein. In some embodiments, the kits include instructions for performing any of the methods described herein. In some instances, the kits include at least one dose of any of the compositions described herein. In some embodiments, the kits include a delivery system (e.g., syringe) for administering any of the compositions described herein.

[0711] Methods of Treatment

[0712] In one aspect, provided herein are methods of treating a subject with a composition herein, e.g., a polypeptide, binding peptide, therapeutic agent, fusion protein, and combinations thereof.

[0713] Various methods of treatment include activating an immune response in the subject.

[0714] Various methods of treatment include treating cancer. In some embodiments, the term cancer refers to cells having the capacity for autonomous growth (i.e., an abnormal state or condition characterized by rapidly proliferating cell growth). Non -limiting examples cancers include prostate cancer, renal cell carcinoma, pancreatic cancer, liver cancer, uterine cancer, bladder cancer, thyroid cancer, ovarian cancer, breast cancer, endometrial cancer, multiple myeloma, melanoma, lymphomas, lung cancers including small cell lung cancer, kidney cancer, colorectal cancer, pancreatic cancer, gastric cancer, and brain cancer. Particular cancers include bladder urothelial carcinoma, breast invasive carcinoma, cholangiocarcinoma, colon adenocarcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, rectum adenocarcinoma, skin cutaneous melanoma, thyroid carcinoma, uterine corpus endometrial carcinoma, and uterine carcinosarcoma.

[0715] Various methods include delivering the composition to the subject. Non-limiting example delivery methods include intratumoral (IT) injection, guided injection to a lymph node, subcutaneous, intramuscular, and tumor embolization via venous catheter. Delivery methods may also be paired with a secondary procedure, which may or may not be related to the condition that the composition is being used to treat. Non-limiting example of procedures that may be paired with delivery of the composition include colonoscopies, endoscopies, or a variety of surgical procedures, which may be open surgical procedures or minimally invasive surgical procedures.

[0716] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject an immunomodulatory polypeptide tethered to a delivery particle, wherein the immunomodulatory polypeptide comprises a binding peptide that binds the immunomodulatory polypeptide to the delivery particle. In some embodiments, the immunomodulatory polypeptide is localized to a target site in the subject. In some embodiments, the immunomodulatory polypeptide does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the immunomodulatory polypeptide not tethered to the delivery particle. Non-limiting example immunomodulatory peptides include interleukins (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF-related apoptosis-inducing ligand (TRAIL), and Interleukin 4 (IL4). In some embodiments, immunomodulatory polypeptide comprises an interleukin. In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 15-16. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the method further comprises delivering to the subject a second immunomodulatory polypeptide, wherein the second immunomodulatory polypeptide comprises a second binding peptide that binds the second immunomodulatory polypeptide to the delivery particle, wherein the second immunomodulatory polypeptide comprises a human leukocyte antigen (HLA) receptor. In some embodiments, the immunomodulatory polypeptide comprises a human leukocyte antigen (HLA) receptor. In some embodiments, the HLA receptor comprises the alpha chain of the HLA receptor. In some embodiments, the HLA receptor comprises the beta chain of the HLA receptor. In some embodiments, the HLA receptor is a Class I or a Class II HLA receptor. In some embodiments, the HLA receptor comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 17-23, 53, 122. In some embodiments, the binding peptide is positioned N- terminal to the HLA receptor. In some embodiments, the binding peptide is positioned C-terminal to the HLA receptor. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101-113, 124-125, 127-128. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106- 108, 112-113, 124-125. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the method further comprises delivering to the subject an antigen associated with a disease or condition of the subject. In some embodiments, the antigen is a tumor antigen. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0717] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0718] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin (IL). In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15, 16, 94, 95, 96, 97, 98, 99, or 100. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C- terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101-113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0719] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin-2 (IL-2). In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 or 15. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, Wil l 3, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0720] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin- 12 (IL- 12). In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 94. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0721] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin- 15 (IL-15). In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 96. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0722] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 24. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0723] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 114. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0724] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 25. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0725] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0726] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 27. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0727] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 28. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0728] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 29. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0729] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 30. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0730] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 31. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0731] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 32. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size. In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 33. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0732] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0733] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 35. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0734] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 54. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0735] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0736] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 56. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0737] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 57. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0738] In some aspects, provided is method of activating an immune response in a subject in need thereof, the method comprising treating the subject with a metabolite comprising an interleukin. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%,

[0739] 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ

[0740] ID NO: 115. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%,

[0741] 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 116. In some embodiments, the interleukin comprises a sequence at least

[0742] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0743] 97%, 98%, or 99% identical to SEQ ID NO: 117. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0744] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 118. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,

[0745] 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 119. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0746] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0747] NO: 120. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%,

[0748] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 121. In some embodiments, the interleukin comprises a sequence at least

[0749] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0750] 97%, 98%, or 99% identical to SEQ ID NO: 126. The metabolite may be released from a larger polypeptide (e.g., a fusion protein herein) after cleavage by a protease. The protease may be furin, caspase, cathepsin, or MMP. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125, 127-128. In some embodiments, the metabolite is localized to a target site in the subject. In some embodiments, the metabolite does not result in systemic activation of the immune response. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some aspects, provided is a method of treating cancer in a subject in need thereof, the method comprising delivering to the subject an immunomodulatory polypeptide tethered to a delivery particle, wherein the immunomodulatory polypeptide comprises a binding peptide that binds the immunomodulatory polypeptide to the delivery particle. In some embodiments, the immunomodulatory polypeptide is localized to a target site in the subject. In some embodiments, the immunomodulatory polypeptide does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the immunomodulatory polypeptide not tethered to the delivery particle. Non-limiting example immunomodulatory peptides include interleukins (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF-related apoptosis-inducing ligand (TRAIL), and Interleukin 4 (IL4). In some embodiments, immunomodulatory polypeptide comprises an interleukin. In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 15-16. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the method further comprises delivering to the subject a second immunomodulatory polypeptide, wherein the second immunomodulatory polypeptide comprises a second binding peptide that binds the second immunomodulatory polypeptide to the delivery particle, wherein the second immunomodulatory polypeptide comprises a human leukocyte antigen (HLA) receptor. In some embodiments, the immunomodulatory polypeptide comprises a human leukocyte antigen (HLA) receptor. In some embodiments, the HLA receptor comprises the alpha chain of the HLA receptor. In some embodiments, the HLA receptor comprises the beta chain of the HLA receptor. In some embodiments, the HLA receptor is a Class I or a Class II HLA receptor. In some embodiments, the HLA receptor comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 17-23, 53, 122. In some embodiments, the binding peptide is positioned N- terminal to the HLA receptor. In some embodiments, the binding peptide is positioned C-terminal to the HLA receptor. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101-113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the method further comprises delivering to the subject an antigen associated with a disease or condition of the subject. In some embodiments, the antigen is a tumor antigen. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0751] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0752] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin (IL). In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15, 16, 94, 95, 96, 97, 98, 99, or 100. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C- terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101-113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size. In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin -2 (IL-2). In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 or 15. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0753] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin- 12 (IL- 12). In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 94. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0754] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein, polypeptide, metabolite, or other composition herein comprising an interleukin- 15 (IL- 15). In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 96. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle, e.g., via a binding peptide of the fusion protein. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments, the binding peptide is positioned N-terminal to the interleukin. In some embodiments, the binding peptide is positioned C-terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the binding peptide is positioned between the first interleukin and the second interleukin. In some embodiments, the binding peptide is connected to the immunomodulatory polypeptide via a linker. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 36-52, 101- 113, 124-125. In some embodiments, the linker comprises a protease cleavage site. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0755] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 24. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0756] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 114. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0757] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 25. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0758] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 26. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0759] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 27. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0760] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 28. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0761] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 29. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0762] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 30. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0763] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 31. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0764] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 32. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0765] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 33. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0766] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 34. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0767] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 35. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0768] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 54. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0769] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0770] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 56. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size.

[0771] In some aspects, provided is method of treating cancer in a subject in need thereof, the method comprising delivering to the subject a fusion protein comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 57. The method may further comprise delivering a particle to the subject, optionally wherein the fusion protein is bound to the particle. In some embodiments, the fusion protein is localized to a target site in the subject. In some embodiments, the fusion protein does not result in systemic activation of the immune response . In some embodiments, the delivery results in fewer side effects than delivery of the fusion protein not bound to the particle. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody. In some embodiments where the method comprises delivery of a particle, the particle comprises a calcium compound. Calcium compounds include, without limitation, calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, and hydroxyapatite. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size. In some aspects, provided is method of activating treating cancer in a subject in need thereof, the method comprising treating the subject with a metabolite comprising an interleukin. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0772] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0773] NO: 115. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%,

[0774] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 116. In some embodiments, the interleukin comprises a sequence at least

[0775] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0776] 97%, 98%, or 99% identical to SEQ ID NO: 117. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%.

[0777] 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 118. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,

[0778] 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 119. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,

[0779] 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID

[0780] NO: 120. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%,

[0781] 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 121. In some embodiments, the interleukin comprises a sequence at least

[0782] 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,

[0783] 97%, 98%, or 99% identical to SEQ ID NO: 126. The metabolite may be released from a larger polypeptide (e.g., a fusion protein herein) after cleavage by a protease. The protease may be furin, caspase, cathepsin, or MMP. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0784] 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125, 127-128. In some embodiments, the metabolite is localized to a target site in the subject. In some embodiments, the metabolite does not result in systemic activation of the immune response. In some embodiments, the method further comprises administering to the subject an immune checkpoint inhibitor, e.g., an anti-PD-1 antibody.

[0785] In some aspects, provided is a method of activating an immune response in a subject in need thereof to treat cancer, the method comprising delivering to the subject an anti -cancer agent bound to a particle comprising a calcium compound. In some aspects, provided is a method of treating cancer in a subject in need thereof, the method comprising delivering to the subject an anti -cancer agent bound to a particle comprising a calcium compound. In some embodiments, the anti-cancer agent is localized to a target site in the subject. In some embodiments, the anti -cancer agent does not result in systemic activation of the immune response. In some embodiments, the delivery results in fewer side effects than delivery of the anti -cancer agent not tethered to the delivery particle. In some embodiments, the method results in immune activation that is specific for the cancer. In some embodiments, the anti-cancer agent comprises a binding peptide that binds to the calcium compound of the particle. In some embodiments, the calcium compound comprises calcium phosphate, calcium carbonate, calcium oxide, calcium silicate, hydroxyapatite, a metal oxide, or an oxygen or nitrogen passivated material. In some embodiments, the calcium compound comprises tricalcium phosphate. In some embodiments, the calcium compound comprises beta-tricalcium phosphate. In some embodiments, the particle is from about 1 micron to about 150 microns in size. In some embodiments, the particle is from about 5 microns to about 50 microns in size. In some embodiments, the particle is about 40 microns in size. In some embodiments, the anti -cancer agent comprises a protease cleavage site. In some embodiments, the protease cleavage site is cleaved by a protease of a T cell. In some embodiments, the protease cleavage site is cleaved by a protease of a cancer cell in the subject. In some embodiments, the protease cleavage site comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 47-50, 106-108, 112-113, 124-125, 127-128. In some embodiments, the method further comprises delivering to the subject an antigen associated with the cancer of the subject (tumor antigen). In some embodiments, the anti -cancer agent is an immunomodulatory polypeptide. Non-limiting example immunomodulatory peptides include interleukins (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF-related apoptosis-inducing ligand (TRAIL), and Interleukin 4 (IL4). In some embodiments, the immunomodulatory polypeptide comprises an interleukin. In some embodiments, the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 15-16. In some embodiments, the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 15, 16, 94, 95, 96, 97, 98, 99, or 100. In some embodiments, anti -cancer agent comprises a binding peptide positioned N-terminal to the interleukin. In some embodiments, the anti-cancer agent comprises a binding peptide positioned C- terminal to the interleukin. In some embodiments, the interleukin comprises a first interleukin and a second interleukin. In some embodiments, the anti -cancer agent comprises a binding peptide positioned between the first interleukin and the second interleukin. In some embodiments, the method further comprises delivering to the subject a second anti -cancer agent, wherein the second anti-cancer agent comprises a second immunomodulatory polypeptide comprising a human leukocyte antigen (HLA) receptor. In some embodiments, the anti -cancer agent comprises a human leukocyte antigen (HLA) receptor. In some embodiments, the HLA receptor comprises the alpha chain of the HLA receptor. In some embodiments, the HLA receptor comprises the beta chain of the HLA receptor. In some embodiments, the HLA receptor is a Class I or a Class II HLA receptor. In some embodiments, the HLA receptor comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 17-23, 53, 122. In some embodiments, the anti -cancer agent comprises a binding peptide positioned N-terminal to the HLA receptor. In some embodiments, the anti -cancer agent comprises a binding peptide positioned C-terminal to the HLA receptor. In some embodiments, the anti-cancer agent comprises a binding peptide bound to the particle. In some embodiments, the binding peptide comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-14. In some embodiments, the method further comprises delivering to the subject an antigen associated with the cancer of the subject. In some embodiments, the antigen is a tumor antigen.

[0786] Methods of Treatment: Combination Therapies

[0787] In one aspect, provided herein are methods of treating a subject with a composition herein, e.g., a polypeptide, binding peptide, therapeutic agent, fusion protein, and combinations thereof.

[0788] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein of Table 3 or a fusion protein having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to any one of the fusion proteins of Table 3, in combination with an antigen peptide, such as an antigen peptide of Table 2, and peptides having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 2.

[0789] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein of Table 3 or a fusion protein having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to any one of the fusion proteins of Table 3, in combination with an immune checkpoint inhibitor. In some non-limiting embodiments, an immune checkpoint inhibitor comprises an antiProgrammed cell death protein 1 (anti-PD-1) antibody, an anti-Programmed death-ligand 1 (anti-PD- Ll) antibody, an anti- Cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) antibody, or combinations thereof. Non-limiting example anti-PDl antibodies include pembrolizumab (e.g., Keytruda), toripalimab, nivolumab (e.g., Opdivo), cemiplimab (e.g., Libtayo), dostarlimab (e.g., Jemperli), cindilimab, camrelizumab, tislelizumab, penpulimab, zimberelimab, prolgolimab, retifanlimab. Non-limiting anti-PD-Ll inhibitors include atezolizumab (e.g., Tecentriq), durvalumab (e.g., Imfinzi), envafolimab, sugemalimab and avelumab (e.g., Bavencio). Non-limiting anti-CTLA-4 inhibitors include ipilimumab (e.g., Yervoy) and tremelimumab.

[0790] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising a fusion protein of Table 3, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a fusion protein of Table 3, in combination with a peptide of Table 2, or a peptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,

[0791] 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 2.

[0792] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 24, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0793] 96%, 97%, 98%, or 99% identity to SEQ ID NO: 24, in combination with a peptide of Table 2, or a peptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 2.

[0794] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 114, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 114, in combination with a peptide of Table 2, or a peptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to peptides of Table 2.

[0795] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 24, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0796] 96%, 97%, 98%, or 99% identity to SEQ ID NO: 24, in combination with an immune checkpoint inhibitor.

[0797] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 24, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%.

[0798] 96%, 97%, 98%, or 99% identity to SEQ ID NO: 24, in combination with an anti-PD-1 antibody. Non-limiting example anti-PDl antibodies include pembrolizumab (e.g., Keytruda), toripalimab, nivolumab (e.g., Opdivo), cemiplimab (e.g., Libtayo), dostarlimab (e.g., Jemperli), cindilimab, camrelizumab, tislelizumab, penpulimab, zimberelimab, prolgolimab, retifanlimab.

[0799] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 24, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0800] 96%, 97%, 98%, or 99% identity to SEQ ID NO: 24, in combination with an anti-PD-Ll antibody.

[0801] Non-limiting anti-PD-Ll inhibitors include atezolizumab (e.g., Tecentriq), durvalumab (e.g., Imfinzi), envafolimab, sugemalimab and avelumab (e.g., Bavencio).

[0802] In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 24, or a fusion protein comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,

[0803] 96%, 97%, 98%, or 99% identity to SEQ ID NO: 24, in combination with an anti-CTLA-4 antibody.

[0804] Non-limiting anti-CTLA-4 inhibitors include ipilimumab (e.g., Yervoy) and tremelimumab. In some embodiments, a method of treating a subject with a composition herein comprises administering to a subject a fusion protein comprising SEQ ID NO: 114 or a fusion protein compris...

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method of activating an immune response and / or treating cancer in a subject in need thereof, the method comprising delivering to the subject an immunomodulatory polypeptide comprising an interleukin, and a particle comprising a calcium compound.

2. The method of claim 1, wherein the immunomodulatory polypeptide comprises a binding peptide that binds the calcium compound of the particle.

3. The method of claim 2, wherein the binding peptide comprises a sequence at least 80% identical to any one of SEQ ID NOS: 12-14 and 1-11.

4. The method of claim 2 or claim 3, wherein the immunomodulatory polypeptide comprises a protease cleavage site positioned between the interleukin and the binding peptide, wherein the protease cleavage site is cleaved by a protease of a T cell and / or a cancer cell.

5. The method of claim 4, wherein the protease cleavage site comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128 and 112-113.

6. The method of any one of claims 2 to 5, wherein the immunomodulatory polypeptide comprises a linker positioned between the interleukin and the binding peptide, wherein the linker comprises (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111, (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105; or (iii) one or more of SEQ ID NOS: 36-52, 124-125, and 101-113.

7. The method of any one of claims 1 to 6, wherein the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 16, 15, and 94-100.

8. The method of any one of claims 1 to 7, wherein the interleukin comprises IL2, IL 12, IL21, IL 15, IL7, IL24, or IL28.

9. The method of any one of claims 1-8, wherein the immunomodulatory polypeptide is localized to a target site in the subject, the immunomodulatory polypeptide does not result in systemic activation of the immune response, delivering to the subject results in fewer side effects thandelivering to the subject the immunomodulatory polypeptide without the particle, and / or the method results in immune activation that is specific for the cancer.

10. The method of any one of claims 1 to 9, comprising administering to the subject an immune checkpoint inhibitor.

11. The method of claim 10, wherein the immune checkpoint inhibitor comprises an anti-PDl antibody.

12. The method of any one of claims 1 to 11, wherein the cancer is melanoma, renal cell carcinoma, pancreatic, colorectal, lung, kidney, liver, uterine, bladder, thyroid, ovarian, or breast cancer.

13. The method of any one of claims 1 to 12, wherein the delivery is via intratumoral (IT) injection, guided injection to a lymph node, subcutaneous, intramuscular, or tumor embolization via venous catheter.

14. The method of any one of claims 1 to 13, wherein the delivery is performed during a surgical procedure, a colonoscopy, or an endoscopy.

15. A composition comprising a calcium compound particle, and a peptide fusion protein comprising a binding peptide connected to an immunomodulatory polypeptide, wherein the binding peptide binds to the calcium compound to tether the peptide fusion protein to the calcium compound particle, optionally wherein the immunomodulatory polypeptide comprises an interleukin (IL), Interferon alpha (IFNa), Interferon alpha-2 (IFNa2), Interferon gamma (IFN-y), Tumor necrosis factor alpha (TNF-a), TNF -related apoptosis-inducing ligand (TRAIL), or Interleukin 4 (IL4).

16. The composition of claim 15, wherein the binding peptide comprises one or more of: a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 12-14 and 1-11.

17. The composition of claim 15 or claim 16, wherein the immunomodulatory polypeptide comprises the interleukin, and the interleukin comprises IL2, IL12, IL21, IL15, IL7, IL24, or IL28.

18. The composition of claim 15 or claim 16, wherein the immunomodulatory polypeptide comprises the interleukin, and the interleukin comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 16, 15 and 94-100.

19. The composition of any one of claims 15 to 18, comprising a linker position between the binding peptide and the immunomodulatory polypeptide, wherein the linker comprises (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 42 and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111, (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 43, asequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%. 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105; or (iii) one or more of SEQ ID NOS: 36- 52, 124-125, and 101-113.

20. The composition of any one of claims 15 to 19, comprising a protease cleavage site positioned between the binding peptide and the immunomodulatory polypeptide, wherein the protease cleavage site comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113.

21. The method of any one of claims 1 to 14, or the composition of any one of claims 15 to 20, wherein the particle is from about 1 micron to about 100 microns in size.

22. The method of any one of claims 1 to 14 or claim 21, or the composition of any one of claims 15 to 21, wherein the calcium compound comprises beta-tricalcium phosphate.

23. A fusion protein of Formula 1, Formula 2, Formula 3, Formula 4, Formula 5, Formula 6, Formula7, Formula 8, Formula 9, Formula 10, Formula 11, or Formula 12:TA - BP (Formula 1),TA - L - BP (Formula 2),BP - TA (Formula 3),BP - L - TA (Formula 4),TAI - LI - BP - L2 - TA2 (Formula 5),TAI - BP - TA2 (Formula 6),TAI - LI - BP - TA2 (Formula 7),TAI - BP - LI - TA2 (Formula 8)BP1 - LI - TA - L2 - BP2 (Formula 9),BP 1 - TA - BP2 (Formula 10),BP1 - LI - TA - BP2 (Formula 11),BP1 - TA - LI - BP2 (Formula 12); wherein each TA, TAI, and TA2 is independently a therapeutic agent; each L, LI, and L2 is independently a linker, and each BP, BP1, and BP2 is independently a binding peptide; and wherein: each therapeutic agent independently comprises: an immunomodulatory agent, an anti -cancer agent, an antigen peptide, or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 16, 15, 17-23, 53, 58-100, and 122;each binding peptide independently comprises a sequence at least 80%, 81%, 82%, 83%,84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 12, 13, 14, 1-11; and each linker independently comprises one or more of: (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 36-52, 124-125, 127-128, and 101-113.

24. A polypeptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 24, 114, 25-35, 55-57, 126, and 115-121.

25. A polypeptide comprising (i) a binding peptide comprising a sequence at least 80%, 81%, 82%,83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or99% identical to SEQ ID NO: 12(ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS) , and (ii) an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16(APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCL EEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR WITFSQSIISTLT).

26. A polypeptide comprising (i) a binding peptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13 (AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWT AAESTSKKRPFS), and (ii) an interleukin-2 comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCL EEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR WITFSQSIISTLT).

27. A polypeptide comprising:(i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16 (APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCL EEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR WITFSQSIISTLT); and(ii)(a) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 12,(b) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13,(c) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 14,(d) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1(ILAETTHHRPWS),(e) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2(STADTSHHRPST),(f) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 3(VGADSTHHRPVT),(g) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 4(LIADSTHHSPWT),(h) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5(AAESTSKKRPFS),(i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7(VIGESTHHRPWS),(j) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10(ILAESTHHKPWT),(k) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 8(IIGESSHHKPFT),(l) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9(GLGDTTHHRPWG),(m) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %. 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 6(LLADTTHHRPWT),(n) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 11, or(o) a combination comprising two or more sequences of (a)-(n).

28. The polypeptide of any one of claims 25 to 27, comprising a linker positioned between (i) and (ii), wherein the linker comprises (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ IDNO: 42 and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 111, (ii) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 103, a sequence at least 80%, 81%,82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98%, or 99% identical to SEQ ID NO: 43, a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 104, and / or a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 105; or (iii) one or more of SEQ ID NOS: 36-52, 124-125, and 101-113.

29. The polypeptide of any one of claims 25 to 27, comprising a protease cleavage site positioned between (i) and (ii), wherein the protease cleavage site comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128, and 112-113.

30. The polypeptide of claim 29, wherein the cleavable linker comprises SEQ ID NO: 106 (RKKR) or SEQ ID NO: 113 (RKKRSTDEVDGAPPLGL).

31. A polypeptide comprising (i) a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13(AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWT AAESTSKKRPFS), (ii) a first interleukin-2, and (iii) a second interleukin-2, wherein each of the first interleukin-2 and the second interleukin-2 independently comprise a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 16(APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCL EEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR WITFSQSIISTLT).

32. The polypeptide of claim 31, wherein (i) is positioned between (ii) the first interleukin-2 and (iii) the second interleukin -2.

33. The polypeptide of claim 31 or claim 32, wherein (i) and (ii) are connected via a first linker, and (i) and (iii) are connected via a second linker.

34. The polypeptide of claim 33, wherein the first linker comprises one or more of SEQ ID NOS: 36- 52, 124-125, 101-113, and the second linker comprises one or more of SEQ ID NOS: 36-52, 124-125, 101-113.

35. The polypeptide of claim 33, wherein the first linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more of SEQ ID NOS: 103, 109, and 104; and the second linker comprises a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one or more of SEQ ID NOS: 103, 109, and 104.

36. The polypeptide of any one of claims 33 to 35, wherein the first linker comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128 and 112-113; and the second linker comprises one or more of (i) a furin cleavage site, (ii) a caspase cleavage site, (iii) a matrix metalloproteinase cleavage site, (iv) a cathepsin cleavage site, and (v) one or more of SEQ ID NOS: 47-50, 106-108, 124-125, 127-128 and 112-113.

37. The polypeptide of any one of claims 33 to 36, wherein the first linker comprises a furin cleavage site and the second linker comprises a furin cleavage site.

38. A polypeptide comprising a sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 13 (AAESTSKKRPFSILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWT AAESTSKKRPFS), SEQ ID NO: 12 (ILAETTHHRPWSSTADTSHHRPSTVGADSTHHRPVTLIADSTHHSPWTAAESTSKKRPFS) , or SEQ ID NO: 14 (LIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTLIADSTHHSPWTL IADSTHHSPWT).

39. A nucleic acid encoding the composition of any one of claims 15-20, the fusion protein of claim 23, or the polypeptide of any one of claims 24-38.

40. A vector comprising the nucleic acid of claim 39.

41. A kit comprising the composition of any one of claims 15-20, the fusion protein of claim 23, or the polypeptide of any one of claims 24-38; and a particle comprising a calcium compound.

42. A method of treating a subject in need thereof, the method comprising delivering to the subject the composition of any one of claims 15-20, the fusion protein of claim 23, the polypeptide of any one of claims 24-38, or the kit of claim 41.

43. The method of claim 42, comprising administering to the subject an immune checkpoint inhibitor.

44. The method of claim 43, wherein the immune checkpoint inhibitor comprises an anti-PDl antibody.

45. The method of any one of claims 42 to 44, wherein the method of treating comprising treating cancer in the subject, wherein the cancer is melanoma, renal cell carcinoma, pancreatic, colorectal, lung, kidney, liver, uterine, bladder, thyroid, ovarian, or breast cancer.

46. The method of any one of claims 42 to 45, wherein the method of treating comprises activating an immune response in the subject.

47. The method of any one of claims 42 to 46, wherein the delivery is via intratumoral (IT) injection, guided injection to a lymph node, subcutaneous, intramuscular, or tumor embolization via venous catheter.

48. The method of any one of claims 42 to 47, wherein the delivery is performed during a surgical procedure, a colonoscopy, or an endoscopy.

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