SIRP gamma antibodies for treatment of epstein–BARR virus infections

Abstract

Provided herein are SIRPγ antibodies that specifically SIRPγ, and which have low or no affinity for binding SIRPα and SIRPβ, for the treatment of Epstein–Barr virus (EBV) and clinically relevant parameters thereof.

Description

Attorney Docket No.: ELTH-011 / 01WO 336159-2069 SIRP GAMMA ANTIBODIES FOR TREATMENT OF EPSTEIN–BARR VIRUS INFECTIONS CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. provisional patent application number 63 / 637,314, filed on April 22, 2024, the contents of which is incorporated by reference herein in its entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (ELTH_011_01WO_SeqList_ST26.xml; Size: 428,246 bytes; and Date of Creation: April 17, 2025) are herein incorporated by reference in its entirety. BACKGROUND

[0003] Epstein-Barr virus (EBV) is a common human virus of the herpesvirus family which infects B cells and also epithelial cells. After infection occurs, EBV can remain dormant for life in the host’s cells and reactivate to produce new virus particles. In many cases EBV may not cause any notable symptoms, especially in young children. However, those individuals that do experience symptoms, experience a wide variety of symptoms ranging from mild to severe. One significant concern with EBV infection is its linkage to several diseases and disorders including a variety of cancers such as lymphoma and immune disorders such as hemophagocytic lymphohistiocytosis (HLH).

[0004] Despite a high prevalence of EBV infection in humans, there is currently no licensed vaccine available, making treatment and management methods highly desirable. Thus, there is a need for novel targets, agents, and protocols for the treatment of EBV infection. Provided herein are methods and compositions that address this need. SUMMARY

[0005] The disclosure provides SIRPγ antibodies that specifically bind SIRP^, wherein the antibody has low or no affinity for binding SIRPα and SIRPβ, useful in a method of treating an EBV infection in a subject in need thereof.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0006] In some embodiments of the antibodies of disclosure, the antibody comprises the heavy and light variable chain CDR sequence combination selected from the group consisting of: (a) SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220; (b) SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226; (c) SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232; (d) SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238; (e) SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244; (f) SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250; (g) SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256; (h) SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262; (i) SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268; (j) SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 271, SEQ ID NO: 272, SEQ ID NO: 273, SEQ ID NO: 274; (k) SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, SEQ ID NO: 278, SEQ ID NO: 279, SEQ ID NO: 280; (l) SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286; (m) SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292; (n) SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298; (o) SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 (p) SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310; (q) SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316; (r) SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322; (s) SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328; (t) SEQ ID NO: 329, SEQ ID NO: 330, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334; (u) SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340; (v) SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 343, SEQ ID NO: 344, SEQ ID NO: 345, SEQ ID NO: 346; (w) SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 350, SEQ ID NO: 351, SEQ ID NO: 352; (x) SEQ ID NO: 353, SEQ ID NO: 354, SEQ ID NO: 355, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 358; (y) SEQ ID NO: 359, SEQ ID NO: 360, SEQ ID NO: 361, SEQ ID NO: 362, SEQ ID NO: 363, SEQ ID NO: 364; (z) SEQ ID NO: 365, SEQ ID NO: 366, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 369, SEQ ID NO: 370; (aa) SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 373, SEQ ID NO: 374, SEQ ID NO: 375, SEQ ID NO: 376; (bb) SEQ ID NO: 377, SEQ ID NO: 378, SEQ ID NO: 379, SEQ ID NO: 380, SEQ ID NO: 381, SEQ ID NO: 382; (cc) SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388; (dd) SEQ ID NO: 389, SEQ ID NO: 390, SEQ ID NO: 391, SEQ ID NO: 392, SEQ ID NO: 393, SEQ ID NO: 394; (ee) SEQ ID NO: 395, SEQ ID NO: 396, SEQ ID NO: 397, SEQ ID NO: 398, SEQ ID NO: 399, SEQ ID NO: 400;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 (ff) SEQ ID NO: 401, SEQ ID NO: 402, SEQ ID NO: 403, SEQ ID NO: 404, SEQ ID NO: 405, SEQ ID NO: 406; (gg) SEQ ID NO: 407, SEQ ID NO: 408, SEQ ID NO: 409, SEQ ID NO: 410, SEQ ID NO: 411, SEQ ID NO: 412; (hh) SEQ ID NO: 413, SEQ ID NO: 414, SEQ ID NO: 415, SEQ ID NO: 416, SEQ ID NO: 417, SEQ ID NO: 418; (ii) SEQ ID NO: 419, SEQ ID NO: 420, SEQ ID NO: 421, SEQ ID NO: 422, SEQ ID NO: 423, SEQ ID NO: 424; (jj) SEQ ID NO: 425, SEQ ID NO: 426, SEQ ID NO: 427, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430; (kk) SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436; (ll) SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, SEQ ID NO: 441, SEQ ID NO: 442; (mm) SEQ ID NO: 443, SEQ ID NO: 444, SEQ ID NO: 445, SEQ ID NO: 446, SEQ ID NO: 447, SEQ ID NO: 448; (nn) SEQ ID NO: 449, SEQ ID NO: 450, SEQ ID NO: 451, SEQ ID NO: 452, SEQ ID NO: 453, SEQ ID NO: 454; (oo) SEQ ID NO: 455, SEQ ID NO: 456, SEQ ID NO: 457, SEQ ID NO: 458, SEQ ID NO: 459, SEQ ID NO: 460; (pp) SEQ ID NO: 461, SEQ ID NO: 462, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466; (qq) SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 470, SEQ ID NO: 471, SEQ ID NO: 472; (rr) SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478; (ss) SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484; (tt) SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490; and (uu) SEQ ID NO: 491, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, SEQ ID NO: 495, SEQ ID NO: 496.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0007] In some embodiments of the antibodies of the disclosure, the heavy chain variable region sequence and the light chain variable region sequence are selected from the group consisting of: (a) the VH comprises the amino acid sequence of SEQ ID NO: 535, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 536, or an amino acid sequence with at least 80% sequence identity thereto; (b) the VH comprises the amino acid sequence of SEQ ID NO: 537, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 538, or an amino acid sequence with at least 80% sequence identity thereto; (c) the VH comprises the amino acid sequence of SEQ ID NO: 539, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 540, or an amino acid sequence with at least 80% sequence identity thereto; (d) the VH comprises the amino acid sequence of SEQ ID NO: 541, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 542, or an amino acid sequence with at least 80% sequence identity thereto; (e) the VH comprises the amino acid sequence of SEQ ID NO: 543, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 544, or an amino acid sequence with at least 80% sequence identity thereto; (f) the VH comprises the amino acid sequence of SEQ ID NO: 545, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 546, or an amino acid sequence with at least 80% sequence identity thereto; (g) the VH comprises the amino acid sequence of SEQ ID NO: 547, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 548, or an amino acid sequence with at least 80% sequence identity thereto; (h) the VH comprises the amino acid sequence of SEQ ID NO: 549, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the aminoAttorney Docket No.: ELTH-011 / 01WO 336159-2069 acid sequence of SEQ ID NO: 550, or an amino acid sequence with at least 80% sequence identity thereto; (i) the VH comprises the amino acid sequence of SEQ ID NO: 551, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 552, or an amino acid sequence with at least 80% sequence identity thereto; (j) the VH comprises the amino acid sequence of SEQ ID NO: 553, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 554, or an amino acid sequence with at least 80% sequence identity thereto; (k) the VH comprises the amino acid sequence of SEQ ID NO: 555, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 556, or an amino acid sequence with at least 80% sequence identity thereto; (l) the VH comprises the amino acid sequence of SEQ ID NO: 557, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 558, or an amino acid sequence with at least 80% sequence identity thereto; (m) the VH comprises the amino acid sequence of SEQ ID NO: 559, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 560, or an amino acid sequence with at least 80% sequence identity thereto; (n) the VH comprises the amino acid sequence of SEQ ID NO: 561, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 562, or an amino acid sequence with at least 80% sequence identity thereto; (o) the VH comprises the amino acid sequence of SEQ ID NO: 563, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 564, or an amino acid sequence with at least 80% sequence identity thereto; (p) the VH comprises the amino acid sequence of SEQ ID NO: 565, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the aminoAttorney Docket No.: ELTH-011 / 01WO 336159-2069 acid sequence of SEQ ID NO: 566, or an amino acid sequence with at least 80% sequence identity thereto; (q) the VH comprises the amino acid sequence of SEQ ID NO: 567, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 568, or an amino acid sequence with at least 80% sequence identity thereto; (r) the VH comprises the amino acid sequence of SEQ ID NO: 569, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 570, or an amino acid sequence with at least 80% sequence identity thereto; (s) the VH comprises the amino acid sequence of SEQ ID NO: 571, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 572, or an amino acid sequence with at least 80% sequence identity thereto; (t) the VH comprises the amino acid sequence of SEQ ID NO: 573, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 574, or an amino acid sequence with at least 80% sequence identity thereto; (u) the VH comprises the amino acid sequence of SEQ ID NO: 575, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 576, or an amino acid sequence with at least 80% sequence identity thereto; (v) the VH comprises the amino acid sequence of SEQ ID NO: 577, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 578, or an amino acid sequence with at least 80% sequence identity thereto; (w) the VH comprises the amino acid sequence of SEQ ID NO: 579, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 580, or an amino acid sequence with at least 80% sequence identity thereto; (x) the VH comprises the amino acid sequence of SEQ ID NO: 581, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the aminoAttorney Docket No.: ELTH-011 / 01WO 336159-2069 acid sequence of SEQ ID NO: 582, or an amino acid sequence with at least 80% sequence identity thereto; (y) the VH comprises the amino acid sequence of SEQ ID NO: 583, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 584, or an amino acid sequence with at least 80% sequence identity thereto; (z) the VH comprises the amino acid sequence of SEQ ID NO: 585, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 586, or an amino acid sequence with at least 80% sequence identity thereto; (aa) the VH comprises the amino acid sequence of SEQ ID NO: 587, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 588, or an amino acid sequence with at least 80% sequence identity thereto; (bb) the VH comprises the amino acid sequence of SEQ ID NO: 589, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 590, or an amino acid sequence with at least 80% sequence identity thereto; (cc) the VH comprises the amino acid sequence of SEQ ID NO: 591, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 592, or an amino acid sequence with at least 80% sequence identity thereto; (dd) the VH comprises the amino acid sequence of SEQ ID NO: 593, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 594, or an amino acid sequence with at least 80% sequence identity thereto; (ee) the VH comprises the amino acid sequence of SEQ ID NO: 595, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 596, or an amino acid sequence with at least 80% sequence identity thereto; (ff) the VH comprises the amino acid sequence of SEQ ID NO: 597, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the aminoAttorney Docket No.: ELTH-011 / 01WO 336159-2069 acid sequence of SEQ ID NO: 598, or an amino acid sequence with at least 80% sequence identity thereto; (gg) the VH comprises the amino acid sequence of SEQ ID NO: 599, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 600, or an amino acid sequence with at least 80% sequence identity thereto; (hh) the VH comprises the amino acid sequence of SEQ ID NO: 601, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 602, or an amino acid sequence with at least 80% sequence identity thereto; (ii) the VH comprises the amino acid sequence of SEQ ID NO: 603, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 604, or an amino acid sequence with at least 80% sequence identity thereto; (jj) the VH comprises the amino acid sequence of SEQ ID NO: 605, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 606, or an amino acid sequence with at least 80% sequence identity thereto; (kk) the VH comprises the amino acid sequence of SEQ ID NO: 607, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 608, or an amino acid sequence with at least 80% sequence identity thereto; (ll) the VH comprises the amino acid sequence of SEQ ID NO: 609, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 610, or an amino acid sequence with at least 80% sequence identity thereto; (mm) the VH comprises the amino acid sequence of SEQ ID NO: 611, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 612, or an amino acid sequence with at least 80% sequence identity thereto; (nn) the VH comprises the amino acid sequence of SEQ ID NO: 613, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the aminoAttorney Docket No.: ELTH-011 / 01WO 336159-2069 acid sequence of SEQ ID NO: 614, or an amino acid sequence with at least 80% sequence identity thereto; (oo) the VH comprises the amino acid sequence of SEQ ID NO: 615, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 616, or an amino acid sequence with at least 80% sequence identity thereto; (pp) the VH comprises the amino acid sequence of SEQ ID NO: 617, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 618, or an amino acid sequence with at least 80% sequence identity thereto; (qq) the VH comprises the amino acid sequence of SEQ ID NO: 619, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 620, or an amino acid sequence with at least 80% sequence identity thereto; (rr) the VH comprises the amino acid sequence of SEQ ID NO: 621, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 622, or an amino acid sequence with at least 80% sequence identity thereto; (ss) the VH comprises the amino acid sequence of SEQ ID NO: 623, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 624, or an amino acid sequence with at least 80% sequence identity thereto; (tt) the VH comprises the amino acid sequence of SEQ ID NO: 625, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 626, or an amino acid sequence with at least 80% sequence identity thereto; and (uu) the VH comprises the amino acid sequence of SEQ ID NO: 627, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 628, or an amino acid sequence with at least 80% sequence identity thereto.

[0008] In some embodiments of the antibodies of the disclosure, the antibody is a monoclonal antibody. In some embodiments, the antibody is an antibody fragment. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is aAttorney Docket No.: ELTH-011 / 01WO 336159-2069 humanized antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a full-length antibody. In some embodiments, the antibody is a bispecific antibody.

[0009] In some embodiments of the antibodies of the disclosure, the Fc domain is selected from the group consisting of human IgG1, IgG2, IgG3, and IgG4. In some embodiments, the Fc domain comprises the amino acid sequence of any one of SEQ ID NO: 15-46. In some embodiments, the Fc domain comprises one or more amino acid substitutions relative to SEQ ID NO: 15 or SEQ ID NO: 39. In some embodiments, the at least one amino acid substitution is at a position selected from the group consisting of: 214, 215, 221, 222, 228, 234, 235, 236, 239, 240, 241, 243, 244, 245, 247, 250, 252, 254, 256, 262, 263, 264, 265, 266, 267, 268, 269, 270, 292, 296, 297, 298, 299, 300, 305, 313, 324, 325, 326, 327, 328, 329, 330, 332, 333, 334, 345, 356, 358, 396, 428, 430, 433, 434, and 440 wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0010] In some embodiments, the EBV infection is acute or chronic. In some embodiments, the subject is infected with an EBV strain selected from the group consisting of type 1 (EBV- 1), type 2 (EBV-2), and an EBV variant strain or subtype thereof. In some embodiments, the subject suffers from an EBV-associated disease or disorder. In some embodiments, the treatment prevents, delays, or mitigates of the onset of an EBV-associated disease or disorder. In some embodiments, the EBV-associated disease or disorder is selected from the group consisting of a secondary hemophagocytic lymphohistiocytosis (sHLH), cancer, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes (T1D), Macrophage activation syndrome (MAS), chronic NK lymphocytosis, and T cell chronic active EBV (CAEBV). In some embodiments, the subject suffers from one or more additional comorbidities.

[0011] In some embodiments, the treatment reduces the EBV viral load in the subject. In some embodiments, the EBV viral load is reduced at least by 10%. In some embodiments, the EBV viral load is reduced in the blood. In some embodiments, the EBV viral load is reduced in B cells, T cells, NK cells, or myeloid cells. In some embodiments, the EBV viral load is reduced in bone marrow. In some embodiments, the treatment results in the depletion of SIRPγ-expressing cells. In some embodiments, the SIRPγ-expressing cells are B cells, T cells, or NK cells. In some embodiments, the method of treatment comprises monitoring EBV viral load, PET-SCANs, C-reactive protein (CRP), sCD25, and / or ferritin peak, minimum,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 maximum, and reduction prospectively to diagnose and predict prognosis, and / or likelihood of response to therapy for the EBV infection, EBV associated disease or disorder, and / or the one or more additional comorbidities.

[0012] In some embodiments, the SIRPγ binding antibody is administered to the subject subcutaneously or intravenously. In some embodiments, the administration occurs in a treatment phase (herein referred to interchangeably as a maintenance phase). In some embodiments, the method comprises more than one treatment phase. In some embodiments, the treatment phase comprises a dose of at least about 0.01 mg / kg to about 5.0 mg / kg of the SIRPγ binding antibody. In some embodiments, the treatment phase comprises a dose about 0.1 mg / kg to about 1.0 mg / kg of the SIRPγ binding antibody.

[0013] In some embodiments, the SIRPγ binding antibody is administered in combination with an additional therapy. In some embodiments, the additional therapy is selected from the group consisting of corticosteroids, antiviral agents (e.g., nucleoside analogues), interleukin- 2, interferon alfa, intravenous immunoglobulins, etoposide, and other chemotherapy agents.

[0014] In some embodiments, the SIRPγ binding antibody is administered in a pharmaceutical composition, wherein the pharmaceutical composition comprises the antibody, and a pharmaceutically acceptable carrier. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIGS.1A-B shows the PK profile and various HLH markers, PD, and blood count response after IV administration of a SIRPα / β / γ binding antibody during the first 71+ days of treatment in patient 602-01 with EBV triggered sHLH.

[0016] FIG.2 shows Ferritin and ALT response to a SIRPα / β / γ binding antibody during the first 57 days of treatment in patient 601-10 with EBV triggered sHLH in the background of Peripheral T-Cell Lymphoma (PTCL).

[0017] FIG.3 shows Ferritin, sCD25, CRP, and ALT response to a SIRPα / β / γ binding antibody during the first 11 days of treatment in patient 609-02 with EBV+ diffuse large B-cell lymphoma (DLBCL),

[0018] FIGS.4A-B shows an increased frequency of SIRP+ B cells in patient US603- EAP001 with EBV-triggered sHLH. FIG.4A depicts a flow cytometry analysis of B cells from a normal healthy volunteer (NHV) (left) and EBV-triggered sHLH patient (right). FIG.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 4B shows the percentage of SIRP+ B cells in NHV (mean ± SD, n=6) and EBV-triggered sHLH patient. DETAILED DESCRIPTION

[0019] Provided herein are antibodies that specifically bind SIRP^, and have low or no affinity for binding SIRPα and SIRPβ, and methods of treating EBV infections using such antibodies. The antibodies may be useful for treating EBV infections by reducing viral load a subject involved in EBV pathology. Definitions

[0020] Where elements are presented in a list format (e.g., in a Markush group), it should be understood that each possible subgroup of the elements is also disclosed, and that any one or more elements can be removed from the list or group.

[0021] It should be understood that, unless clearly indicated, in any method described or disclosed herein that includes more than one act, the order of the acts is not necessarily limited to the order in which the acts of the method are recited, but the disclosure encompasses exemplary embodiments in which the order of the acts is so limited.

[0022] The terms used throughout the specification are defined as follows unless otherwise limited in specific instances. As used in the specification and the claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. All technical and scientific terms, acronyms, and abbreviates used in the specification and claims have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains, unless defined or stated otherwise. All numerical ranges are inclusive of the values defining the range as well as all integer values in between, unless indicated or defined otherwise.

[0023] The term “priming dose phase” refers to a phase to prime the subject for a subsequent treatment phase. In some embodiments, the dosing protocol comprises a priming dose phase followed by a subsequent treatment phase. In some embodiments, the protocol comprises multiple treatment phases, each optionally preceded by a priming dose phase. The term “priming dose” or “priming doses” refers to one or more doses within the priming dose phase. In some embodiments, a therapeutic effect may be present during the priming dose phase.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0024] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. I. Antibodies A. SIRP^ Antibodies

[0025] Provided herein are antibodies that specifically bind SIRP^, and have low or no affinity for binding SIRPα and SIRPβ (also known as SIRPβ1), and are interchangeably referred to herein as SIRP^ antibodies, anti-SIRP^ antibodies, SIRP^ binding antibodies and the like.

[0026] The term antibody as used herein throughout is used in the broadest sense and includes a monoclonal antibody, polyclonal antibody, human antibody, humanized antibody, non-human antibody, chimeric antibody, a monovalent antibody, and an antibody fragment.

[0027] In exemplary embodiments, the SIRP^ antibodies provided herein are monoclonal antibodies (mAbs). In exemplary embodiments, the SIRP^ antibodies provided herein are human antibodies. In exemplary embodiments, the SIRP^ antibodies provided herein are humanized antibodies. In exemplary embodiments, the SIRP^ antibodies provided herein are monoclonal human antibodies. In exemplary embodiments, the SIRP^ antibodies provided herein are chimeric antibodies. In exemplary embodiments, the SIRP^ antibodies provided herein are monoclonal chimeric antibodies.

[0028] In some embodiments, the SIRPγ antibodies provided herein are antibody fragments, retaining SIRPγ antigen binding specificity. In some embodiments, the antibody fragments are antigen-binding fragments (Fab), variable fragments (Fv) containing VH and VL sequences, single chain variable fragments (scFv) containing VH and VL sequences linked together in one chain, single chain antibody fragments (scAb) or other antibody variable region fragments, such as Fab’, F(ab’)2, dsFv diabody, and Fd polypeptide fragments.

[0029] As used herein, “SIRP^” includes all isoforms, from any species. In the human, there are multiple SIRP^ transcripts, including a full length, two alternatively spliced forms that lack significant portions of their extracellular domains, and one alternatively spliced form that lacks the signal peptide sequence.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0030] The amino acid sequence of hSIRPγ isoform 1 (full length) is provided as SEQ ID NO: 1 (referencing UniProtKB ID Q9P1W8 Isoform 1). 1 MPVPASWPHP PGPFLLLTLL LGLTEVAGEE ELQMIQPEKL LLVTVGKTAT LHCTVTSLLP 61 VGPVLWFRGV GPGRELIYNQ KEGHFPRVTT VSDLTKRNNM DFSIRISSIT PADVGTYYCV 121 KFRKGSPENV EFKSGPGTEM ALGAKPSAPV VLGPAARTTP EHTVSFTCES HGFSPRDITL 181 KWFKNGNELS DFQTNVDPTG QSVAYSIRST ARVVLDPWDV RSQVICEVAH VTLQGDPLRG 241 TANLSEAIRV PPTLEVTQQP MRVGNQVNVT CQVRKFYPQS LQLTWSENGN VCQRETASTL 301 TENKDGTYNW TSWFLVNISD QRDDVVLTCQ VKHDGQLAVS KRLALEVTVH QKDQSSDATP 361 GPASSLTALL LIAVLLGPIY VPWKQKT (SEQ ID NO: 1)

[0031] The amino acid sequence of a splice variant hSIRPγ (isoform 2) is provided as SEQ ID NO: 37. (referencing UniProtKB ID Q9P1W8 Isoform 2). MIQPEKLLLVTVGKTATLHCTVTSLLPVGPVLWFRGVGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISS ITPADVGTYYCVKFRKGSPENVEFKSGPGTEMALGAKPSAPVVLGPAARTTPEHTVSFTCESHGFSPRDITLKWF KNGNELSDFQTNVDPTGQSVAYSIRSTARVVLDPWDVRSQVICEVAHVTLQGDPLRGTANLSEAIRVPPTLEVTQ QPMRVGNQVNVTCQVRKFYPQSLQLTWSENGNVCQRETASTLTENKDGTYNWTSWFLVNISDQRDDVVLTCQVKH DGQLAVSKRLALEVTVHQKDQSSDATPGPASSLTALLLIAVLLGPIYVPWKQKT (SEQ ID NO: 2)

[0032] The amino acid sequence of a splice variant hSIRPγ (isoform 3) is provided as SEQ ID NO: 2. (referencing UniProtKB ID Q9P1W8 Isoform 3). MPVPASWPHPPGPFLLLTLLLGLTEVAGEEELQMIQPEKLLLVTVGKTATLHCTVTSLLPVGPVLWFRGVGPGRE LIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISSITPADVGTYYCVKFRKGSPENVEFKSGPGTEMALGGPASSLT ALLLIAVLLGPIYVPWKQKT (SEQ ID NO: 3)

[0033] The amino acid sequence of another splice variant hSIRPγ (isoform 4) is provided as SEQ ID NO: 3 (referencing UniProtKB ID Q9P1W8 Isoform 4). MPVPASWPHPPGPFLLLTLLLGLTEVAGEEELQMIQPEKLLLVTVGKTATLHCTVTSLLPVGPVLWFRGVGPGRE LIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISSITPADVGTYYCVKFRKGSPENVEFKSGPGTEMALGAKPSAPV VLGPAARTTPEHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPTGQSVAYSIRSTARVVLDPWDVRSQVI CEVAHVTLQGDPLRGTANLSEAIRGPASSLTALLLIAVLLGPIYVPWKQKT (SEQ ID NO: 4)

[0034] The amino acid sequence of cynomolgus monkey SIRPγ is provided as SEQ ID NO: 4. (referencing GenBank: EHH65481.1). MPVPASWSHPPGPFLLLTLLLGFTEVAGEEELQMIQPEKLLLVAVGESATLNCTVTSLLPVGPVLWFRGVGPGRE LIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISSITPADAGTYYCVKFRKGSPENVEFKSGPGTEMALRAKPSAPV VSGPAARATPEHTVSFTCKSHGFSPRDITLKWFKNGNELSDFQTNVDPAGQSVSYSIRSTARVVLAPWDVRSQVT CEVAHVTLQGDPLRGTANLSEAIRVPPTLEVTQQPMRAGNQVNITYQVRNFYPQNLQLTWLENGNVCRTETASTL TENKDGTYNWTSWLLVNTSDQRDDVVLTCQVKHDGQLAVNKSLVLEVSAHQKDQSSDATHGPASSLTVLLLIAVL LGPIYVPWKQKS (SEQ ID NO: 5)

[0035] Accordingly, the SIRPγ antibodies of the disclosure may bind to one or more isoforms of a SIRPγ of a single species. In some embodiments, the SIRPγ antibodies also bind to one or more isoforms of a SIRP^ of more than one species. In some embodiments, the SIRPγ antibodies bind to one or more isoforms of human SIRP^. In some embodiments, the SIRPγ antibodies also bind to one or more isoforms of a non-human primate SIRP^, e.g. a cynomolgus monkey SIRP^.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0036] In some embodiments, the SIRPγ antibodies bind to a plurality of SIRPγ variants or isoforms found in a particular species, e.g. the SIRPγ antibodies bind to more than one of SIRPγ human isoforms 1-3. In some embodiments, the SIRPγ antibodies bind the extracellular domain of SIRPγ (e.g. amino acids 1-360 of SEQ ID NO: 1).

[0037] In some embodiments, a SIRPγ antibody of the disclosure binds to a plurality of SIRPγ isoforms found in a particular species, e.g. the SIRPγ antibody binds to more than one SIRPγ human isoform (e.g. the antibody binds to the full length and one or more splice variants). In other embodiments, the SIRPγ antibody binds to a some but not all SIRPγ isoforms found in a particular species (e.g. the SIRPγ antibody binds to one splice variant, but not all).

[0038] The skilled artisan will recognize that antibodies that exhibit little or no binding to a target antigen can be described as having a low affinity, and a high equilibrium dissociation constant (KD) for the target antigen, for example a KD of about 10 μM or greater, about 100 μM or greater, about 1 mM or greater, or about 10 mM or greater. The skilled artisan will also recognize that antibodies that exhibit little or no binding to a target antigen can be described as having a low affinity, and a high equilibrium dissociation constant (KD) for the target antigen, for example a KD of about 10 μM or greater, about 100 μM or greater, about 1 mM or greater, or about 10 mM or greater. For example, a SIRPγ antibody that binds to SIRPγ may bind to SIRPβ and / or SIRPα with low affinity. A SIRPγ antibody of the disclosure with low affinity for SIRPβ and / or SIRPα may bind to SIRPβ and / or SIRPα with a KD of about 10 μM or greater, about 100 μM or greater, about 1 mM or greater, or about 10 mM or greater but retain higher binding affinity for SIRP^.

[0039] Also provided herein are Fc-containing SIRPγ antibodies. In some embodiments, Fc domain of (interchangeably referred to as a Fc sequence, Fc region, or simply Fc) of the SIRPγ antibody is a human Fc domain. In some embodiments, the Fc domain of a SIRPγ antibody is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the Fc domain of a SIRPγ antibody is that of a mouse. In some embodiments, the Fc domain of a SIRPγ antibody is mouse IgG1 or mouse IgG2a. In some embodiments, the Fc domain of a SIRPγ antibody is that of a rat. In some embodiments, the Fc domain of a SIRPγ antibody is rat IgG1 or rat IgG2b. In embodiments, the Fc domain of a SIRPγ antibody is that of a non- human primate, e.g. it is a cynomolgus monkey Fc domain.

[0040] In some embodiments, the SIRPγ antibodies provided herein are full-length antibodies (comprising an intact tetrameric antibody containing two light chains and two heavy chains,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 each with a variable region, and a constant region). In some embodiments, the constant region of the full-length SIRPγ antibodies comprises a human Fc domain. In some embodiments, the Fc domain of a full-length SIRPγ antibody is from a human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the Fc domain of a full-length SIRPγ antibody is that of a mouse immunoglobulin. In some embodiments, the Fc domain of a full-length SIRPγ antibody is that of a mouse IgG1 or mouse IgG2a. In some embodiments, the Fc domain of a full-length SIRPγ antibody is that of a rat. In some embodiments, the Fc domain of a full-length SIRPγ antibody is from a rat IgG1 or rat IgG2b. In embodiments, the Fc domain of a full-length SIRPγ antibody is that of a non-human primate, e.g. it is a cynomolgus monkey Fc domain.

[0041] In some embodiments, the binding of the Fc-containing antibody to a SIRPγ- expressing cell can mediate effector cell-mediated depletion of the SIRPγ-expressing cell. In some embodiments, the Fc domain of a SIRPγ antibody is a human IgG1 Fc. Exemplary, but non-limiting, sequences of heavy chain constant regions (CH) of human IgG1 encompassing Fc domains of interest are provided as SEQ ID NO: 15-38. SEQ ID NO: 15 provides the canonical human IgG1 heavy chain constant region (CH) sequence. 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 15) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 16) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLAG 121 PDVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPEEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 17) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLAG 121 PDVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPEEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 18) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGGAttorney Docket No.: ELTH-011 / 01WO 336159-2069 PDVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPEEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 19) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPEEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 20) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PDVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 21) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 22) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV LHEALHNHYT QKSLSLSPGK (SEQ ID NO: 23) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHSHYT QKSLSLSPGK (SEQ ID NO: 24) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV LHEALHNHYT QKSLSLSPGK (SEQ ID NO: 25) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHSHYT QKSLSLSPGK (SEQ ID NO: 26) ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 27)Attorney Docket No.: ELTH-011 / 01WO 336159-2069 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 28) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSREE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 29) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE 241 MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 30) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE 241 MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 31) 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPEEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 32)

[0042] In some embodiments, the constant region of human IgG1 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 33, wherein X1 is V or A. 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKXEP KSCDKTHTCP PCPAPELLAG 121 PDVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPEEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 33)

[0043] In some embodiments, the constant region of human IgG1 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 34, wherein X1 is V or A; X2 is G or A; X3 is S or D; and X4 is I or E. 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKXEP KSCDKTHTCP PCPAPELLXG 121 PXVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPXEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 34)Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0044] In some embodiments, the constant region of human IgG1 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 35, wherein X1 is V or A. 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKXEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV LHEALHSHYT QKSLSLSPGK (SEQ ID NO: 35)

[0045] In some embodiments, the constant region of human IgG1 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 36, wherein X1 is V or A; X2 is M or L; and X3 is N or S. 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKXEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRDE 241 LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV XHEALHXHYT QKSLSLSPGK (SEQ ID NO: 36)

[0046] In some embodiments, the constant region of human IgG1 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 37, wherein X1 is K or R; X2 is D or E; and X3 is L or M. 1 ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS 61 GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKXVEP KSCDKTHTCP PCPAPELLGG 121 PSVFLFPPKP KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 181 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ VYTLPPSRXE 241 XTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY SKLTVDKSRW 301 QQGNVFSCSV MHEALHNHYT QKSLSLSPGK (SEQ ID NO: 37)

[0047] In some embodiments, the constant region of human IgG1 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 38, and comprises L234A, L235A, P329G substitutions (referred to as LALA-PG substitutions). ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQ PREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 38)

[0048] In some embodiments, the Fc domain of a Fc-containing SIRPγ antibody is a human IgG4 Fc. Exemplary, but non-limiting, sequences of heavy chain constant regions (CH) of human IgG4 encompassing Fc domains of interest are provided as SEQ ID NO: 39-46. SEQ ID NO: 39 provides the canonical human IgG4 heavy chain constant region (CH) sequence.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 39) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 40) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 41) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 42) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEALGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 43) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 44) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPRE PQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 45)

[0049] In some embodiments, the constant region of human IgG4 heavy chain sequence encompassing a Fc domain of interest is SEQ ID NO: 46, wherein X1 is S or P; AND X2 is L or E. ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPX1CPAPEFX2GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQ EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 46)

[0050] In some embodiments, the SIRPγ antibodies provided herein are chimeric and comprise a variable region from one species, and a constant region from another species, e.g. comprise a human variable region and a mouse constant region. In some embodiments, theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 mouse constant region is mouse IgG1, or mouse IgG2a. In some embodiments, the antibodies comprise a human variable region and a human constant region. In exemplary embodiments, the human constant region comprises sequences from human IgG1, human IgG2, human IgG3, or human IgG4.

[0051] The EU numbering scheme is one of many available antibody numbering schemes based on the residue numbers assigned to a canonical antibody sequence. Accordingly, a skilled artisan would understand that reference to a particular residue using the EU numbering scheme may or may not be exactly the residue in one of the SIRPγ antibodies of the disclosure. For example, if a SIRPγ antibody of the disclosure comprises a V215A substitution in the Fc, wherein the position number of the amino acid residue is of the EU numbering scheme, the residue may not be the actual residue 215 in that particular SIRPγ antibody. It may be actual residue number 213, or 214, or 215, or 216 or others. Accordingly, a skilled artisan will understand how to correspond the recited residue using the EU numbering scheme, to the actual residue in a SIRPγ antibody of the disclosure. The EU numbering system for antibodies is known in the art and is described, for example, at imgt.org / IMGTScientificChart / Numbering / Hu_IGHGnber.html.

[0052] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG1 constant heavy chain (e.g. SEQ ID NO: 15), and heavy chain Fc substitutions are introduced to increase effector function (e.g. those that exhibit increased affinity to Fc^R or promote complement protein binding).

[0053] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG1 constant heavy chain (e.g. SEQ ID NO: 15), and heavy chain Fc substitutions are introduced to decrease effector function (e.g. silence).

[0054] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG1 constant heavy chain (e.g. SEQ ID NO: 15), and heavy chain Fc substitutions are introduced to increase antibody half-life.

[0055] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG4 constant heavy chain (e.g. SEQ ID NO: 39), and heavy chain Fc substitutions are introduced to increase effector function (e.g. those that exhibit increased affinity to Fc^R or promote complement protein binding).Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0056] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG4 constant heavy chain (e.g. SEQ ID NO: 39), and heavy chain Fc substitutions are introduced to decrease effector function (e.g. silence).

[0057] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG4 constant heavy chain (e.g. SEQ ID NO: 39), and heavy chain Fc substitutions are introduced to increase antibody half-life.

[0058] In some embodiments, the Fc domain of a SIRPγ antibody is an IgG1 Fc domain (e.g. the Fc domain from any one of the IgG1 constant heavy chain sequences of SEQ ID NOS: 15-38) or is an IgG4 human Fc domain (e.g. the Fc domain from any one of the IgG4 constant heavy chain sequences of SEQ ID NOS: 39-46).

[0059] In some embodiments, the Fc domain of a SIRPγ antibody is an IgG1 Fc domain (e.g. the Fc domain from any one of the IgG1 constant heavy chain sequences of SEQ ID NOS: 15-38) or is an IgG4 human Fc domain (e.g. the Fc domain from any one of the IgG4 constant heavy chain sequences of SEQ ID NOS: 39, 40, or 46), and comprises at least one amino acid substitution in the heavy chain at a position selected from the group consisting of: 214, 215, 221, 222, 228, 234, 235, 236, 239, 240, 241, 243, 244, 245, 247, 250, 252, 254, 256, 262, 263, 264, 265, 266, 267, 268, 269, 270, 292, 296, 297, 298, 299, 300, 305, 313, 324, 325, 326, 327, 328, 329, 330, 332, 333, 334, 345, 356, 358, 396, 428, 430, 433, 434, and 440 wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0060] In some embodiments, the Fc domain of a SIRPγ antibody is from heavy chain SEQ ID NOS: 15-38, optionally with one or more heavy chain Fc amino acid substitutions, for example at least one amino acid substitution at a position selected from the group consisting of: 214, 215, 221, 222, 228, 234, 235, 236, 239, 240, 241, 243, 244, 245, 247, 250, 252, 254, 256, 262, 263, 264, 265, 266, 267, 268, 269, 270, 292, 296, 297, 298, 299, 300, 305, 313, 324, 325, 326, 327, 328, 329, 330, 332, 333, 334, 345, 356, 358, 396, 428, 430, 433, 434, and 440 wherein the position numbers of the amino acid residues are of the EU numbering scheme. Exemplary substitutions include one or more of K214R, V215A, G236A, S239D, I332E, D356E, L358M, M428L, N434S, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0061] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG1 constant heavy chain (e.g. SEQ ID NO: 15-38), and heavy chain Fc substitutions areAttorney Docket No.: ELTH-011 / 01WO 336159-2069 introduced to, among other effects, increase effector function (e.g. one or more of FcR binding on an immune effector cell, and binding to complement C1q), selected from the group consisting of V215A, G236A, S239D, I332E, G236A / S239D, G236A / I332E, S239D / I332E, V215A / G236A / S239D / I332E, G236A / S239D / I332E, V215A / G236A / S239D / I332E, K326W / E333S, S267E / H268F / S324T, E345R, E430G, E345K, S440Y, K326W, E333S, S267E, H268F, S324T, and E345R / E430G / S440Y, F243L / R292P / Y300L / V305I / P396L, S239D / I332E, S298A / E333A / K334A, L234Y / L235Q / G236W / S239M / H268D / D270E / S298A, and D270E / K326D / A330M / K334E wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0062] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG1 constant heavy chain (e.g. SEQ ID NO: 15-38), and heavy chain Fc substitutions are introduced to reduce (e.g. silence) effector function, including one or more of N297A, N297Q, N297G, L235E, L234A, L235A, K214R, P329G, D356E, and L358M, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0063] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG1 constant heavy chain (e.g. SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 38), and heavy chain Fc substitutions are introduced to reduce effector function (e.g. silence), including L234A, L235A, and P329G, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0064] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG4 constant heavy chain (e.g. SEQ ID NOS: 39, 40 or 46), and heavy chain Fc substitutions are introduced to reduce effector function, including one or more of L235E, and F234A / L235A, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0065] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG2 constant heavy chain, and heavy chain Fc substitutions are introduced to reduce effector function, including H268Q / V309L / A330S / P331S and V234A / G237A / P238S / H268A / V309L / A330S / P331S, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0066] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG4 constant heavy chain (e.g. SEQ ID NO: 39), and the antibody is prone to the dynamic process of Fab-arm exchange. Accordingly, in some embodiments the IgG4 heavy chain Fc domainAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises a S228P substitution, resulting in the reduction of Fab-arm exchange, wherein the position number of the amino acid residues are of the EU numbering scheme.

[0067] In some embodiments, the Fc domain of a SIRPγ antibody is from a human IgG4 constant heavy chain (e.g. SEQ ID NO: 39, 40 or 46), and one or more of the following heavy chain Fc substitution are introduced to reduce effector function: L235A, L235E, S228P, L235E / S228P, S228P / F234A, S228P / F234A / L235A, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0068] In other embodiments, the Fc domain of a SIRPγ antibody is altered to increase its serum half-life. Such alterations include heavy chain Fc substitutions of a human IgG1, IgG2, IgG3 or IgG4 such as M428L, N343S, T250Q / M428L, M252Y / S254T / T256E, M428L / N434S, S267E / L328F, N325S / L328F, and H433K / N434F, wherein the position number of the amino acid residues are of the EU numbering scheme. i. Exemplary SIRPγ antibodies – Complementarity Determining Region (CDR) Sequences

[0069] Provided herein are sequences for exemplary SIRP^ antibodies of the disclosure that specifically bind SIRP^, and have low or no affinity for binding SIRPα and SIRPβ. As referred below, a light chain variable (VL) domain CDR1 region is referred to as CDR-L1; a VL CDR2 region is referred to as CDR-L2; a VL CDR3 region is referred to as CDR-L3; a heavy chain variable (VH) domain CDR1 region is referred to as CDR-H1; a VH CDR2 region is referred to as CDR-H2; and a VH CDR3 region is referred to as CDR-H3. Table 1 provides exemplary CDR triplets for the light chains and heavy chains of SIRPγ antibodies of the disclosure. In some embodiments, the antibodies of the disclosure comprise, 1, 2, 3, or 4 modifications to any CDR sequence of Table 1. Table 1: Exemplary SIRPγ antibody CDR Combinations L Y Y DAttorney Docket No.: ELTH-011 / 01WO 336159-2069 Y M G W Y G S YAttorney Docket No.: ELTH-011 / 01WO 336159-2069Attorney Docket No.: ELTH-011 / 01WO 336159-2069 R A W G G Y W Y Y I W Y D S F D D VAttorney Docket No.: ELTH-011 / 01WO 336159-2069 G R W Y P W Y Y Y L Y M

[0070] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 215, 216, 217, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 218, 219, 220.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0071] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 221, 222, 223, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 224, 225, 226.

[0072] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 227, 228, 229, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 230, 231, 232.

[0073] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 233, 234, 235, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 236, 237, 238.

[0074] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 239, 240, 241, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 242, 243, 244.

[0075] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 245, 246, 247, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 248, 249, 250.

[0076] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 251, 252, 253, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 254, 255, 256.

[0077] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 257, 258, 259, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 260, 261, 262.

[0078] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 263, 264, 265, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 266, 267, 268.

[0079] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 269, 270, 271, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 272, 273, 274.

[0080] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 275, 276, 277, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 278, 279, 280.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0081] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 281, 282, 283, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 284, 285, 286.

[0082] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 287, 288, 289, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 290, 291, 292.

[0083] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 293, 294, 295, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 296, 297, 298.

[0084] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 299, 300, 301, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 302, 303, 304.

[0085] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 305, 306, 307, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 308, 309, 310.

[0086] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 311, 312, 313, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 314, 315, 316.

[0087] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 317, 318, 319, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 320, 321, 322.

[0088] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 323, 324, 325, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 326, 327, 328.

[0089] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 329, 330, 331, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 332, 333, 334.

[0090] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 335, 336, 337, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 338, 339, 340.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0091] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 341, 342, 343, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 344, 345, 346.

[0092] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 347, 348, 349, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 350, 351, 352.

[0093] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 353, 354, 355, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 356, 357, 358.

[0094] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 359, 360, 361, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 362, 363, 364.

[0095] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 365, 366, 367, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 368, 369, 370.

[0096] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 371, 372, 373, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 374, 375, 376.

[0097] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 377, 378, 379, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 380, 381, 382.

[0098] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 383, 384, 385, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 386, 387, 388.

[0099] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 389, 390, 391, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 392, 393, 394.

[0100] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 395, 396, 397, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 398, 399, 400.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0101] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 401, 402, 403, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 404, 405, 406.

[0102] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 407, 408, 409, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 410, 411, 412.

[0103] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 413, 414, 415, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 416, 417, 418.

[0104] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 419, 420, 421, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 422, 423, 424.

[0105] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 425, 426, 427, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 428, 429, 430.

[0106] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 431, 432, 433, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 434, 435, 436.

[0107] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 437, 438, 439, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 440, 441, 442.

[0108] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 443, 444, 445, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 446, 447, 448.

[0109] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 449, 450, 451, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 452, 453, 454.

[0110] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 455, 456, 457, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 458, 459, 460.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0111] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 461, 462, 463, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 464, 465, 466.

[0112] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 467, 468, 469, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 470, 471, 472.

[0113] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 473, 474, 475, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 476, 477, 478.

[0114] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 479, 480, 481, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 482, 483, 484.

[0115] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 485, 486, 487, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 488, 489, 490.

[0116] In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 491, 492, 493, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 494, 495, 496. ii. Exemplary SIRPγ antibodies - Variable Region Sequences

[0117] The term variable region and variable domain are used interchangeably and refer to the portions of the light and heavy chains of an antibody that include the complementarity determining regions and framework regions (FRs).

[0118] Table 2 provides amino acid sequences for the variable domains of an exemplary SIRP^ antibody of the disclosure that specifically bind SIRP^, and have low or no affinity for binding SIRPα and SIRPβ1.

[0119] In some embodiments, a SIRP^ antibody of the disclosure comprises the combination of VH / VL variable chain sequences of any antibody presented in Table 2. In some embodiments, a SIRP^ antibody of the disclosure consist of the combination of VH / VL variable chain sequences of any antibody presented in Table 2.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 Table 2: Exemplary Variable Heavy Chain and Variable Light Chain Amino Acid Sequence Combinations S A A Q SI T T D S R F EQ DI ET T D TI ET T ID NI G T L A EA I L A E EIAttorney Docket No.: ELTH-011 / 01WO 336159-2069 G E A GI S T D SI T D GI H A I S T D S Y L E DI S T D L G K GI N TAttorney Docket No.: ELTH-011 / 01WO 336159-2069 QGI LET FAT Q ID QSI LPT FAT D QS TLE FA Q QSI QS FAT Q ID QGI LD DFA EQ QSI TRA FA EQ QDI LET FAT Q ID QS LIY ISSL RLEI QSI LQS FAT Q IDAttorney Docket No.: ELTH-011 / 01WO 336159-2069 GQSI LQS FAT Q QSL YLA VE RLEI QSL YDA VEA VEI QGI LQS FAT Q ID QSI LES FAT Q ID QS LIY ISSL KLE QS RA FA EQ SQS LIY ISS TRL QSL YAA VEA EIKAttorney Docket No.: ELTH-011 / 01WO 336159-2069 S IY SL V SI ET AT ID S RA A Q SI S AT ID DI QT AT RI QS AT ID SI ES AT S IY SL V SI QG ATAttorney Docket No.: ELTH-011 / 01WO 336159-2069 QGI LQS AT Q QSI LES AT Q QS RA FA EQ

[0120] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 535 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 536, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 535, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 536. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 535, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 536. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 215, 216, 217, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 218, 219, 220.

[0121] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 537 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acidAttorney Docket No.: ELTH-011 / 01WO 336159-2069 sequence of SEQ ID NO: 538, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 537, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 538. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 537, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 538. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 221, 222, 223, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 224, 225, 226.

[0122] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 539 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 540, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 539, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 540. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 539, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 540. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 227, 228, 229, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 230, 231, 232.

[0123] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 541 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 542, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 antibody comprises the amino acid sequence of SEQ ID NO: 541, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 542. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 541, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 542. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 233, 234, 235, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 236, 237, 238.

[0124] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 543 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 544, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 543, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 544. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 543, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 544. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 239, 240, 241, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 242, 243, 244.

[0125] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 545 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 546, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 545, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 546. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acidAttorney Docket No.: ELTH-011 / 01WO 336159-2069 sequence of SEQ ID NO: 545, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 546. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 245, 246, 247, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 248, 249, 250.

[0126] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 547 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 548, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 547, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 548. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 547, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 548. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 251, 252, 253, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 254, 255, 256.

[0127] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 549 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 550, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 549, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 550. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 549, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 550. In some embodiments, the light chain variableAttorney Docket No.: ELTH-011 / 01WO 336159-2069 domain comprises CDR sequences of SEQ ID NOS: 257, 258, 259, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 260, 261, 262.

[0128] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 551 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 552, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 551, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 552. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 551, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 552. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 263, 264, 265, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 266, 267, 268.

[0129] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 553 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 554, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 553, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 554. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 553, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 554. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 269, 270, 271, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 272, 273, 274.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0130] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 555 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 556, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 555, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 556. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 555, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 556. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 275, 276, 277, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 278, 279, 280.

[0131] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 557 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 558, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 557, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 558. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 557, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 558. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 281, 282, 283, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 284, 285, 286.

[0132] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 559 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 560, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 559, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 560. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 559, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 560. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 287, 288, 289, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 290, 291, 292.

[0133] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 561 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 562, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 561, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 562. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 561, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 562. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 293, 294, 295, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 296, 297, 298.

[0134] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 563 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 564, or an amino acid sequence with at least 80%, 81%, 82%, 83%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 563, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 564. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 563, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 564. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 299, 300, 301, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 302, 303, 304.

[0135] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 565 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 566, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 565, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 566. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 565, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 566. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 305, 306, 307, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 308, 309, 310.

[0136] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 567 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 568, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 567, and the light chain variableAttorney Docket No.: ELTH-011 / 01WO 336159-2069 domain of the antibody comprises the amino acid sequence of SEQ ID NO: 568. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 567, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 568. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 311, 312, 313, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 314, 315, 316.

[0137] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 569 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 570, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 569, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 570. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 569, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 570. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 317, 318, 319, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 320, 321, 322.

[0138] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 571 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 572, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 571, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 572. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 571, and the light chain variable domain of the antibody comprisesAttorney Docket No.: ELTH-011 / 01WO 336159-2069 the amino acid sequence of SEQ ID NO: 572. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 323, 324, 325, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 326, 327, 328.

[0139] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 573 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 574, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 573, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 574. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 573, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 574. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 329, 330, 331, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 332, 333, 334.

[0140] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 575 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 576, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 575, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 576. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 575, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 576. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 335, 336, 337, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 338, 339, 340.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0141] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 577 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 578, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 577, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 578. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 577, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 578. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 341, 342, 343, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 344, 345, 346.

[0142] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 579 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 580, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 579, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 580. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 579, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 580. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 347, 348, 349, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 350, 351, 352.

[0143] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 581 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 582, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 581, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 582. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 581, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 582. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 353, 354, 355, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 356, 357, 358.

[0144] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 583 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 584, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 583, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 584. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 583, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 584. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 359, 360, 361, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 362, 363, 364.

[0145] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 585 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 586, or an amino acid sequence with at least 80%, 81%, 82%, 83%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 585, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 586. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 585, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 586. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 365, 366, 367, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 368, 369, 370.

[0146] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 587 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 588, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 587, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 588. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 587, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 588. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 371, 372, 373, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 374, 375, 376.

[0147] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 589 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 590, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 589, and the light chain variableAttorney Docket No.: ELTH-011 / 01WO 336159-2069 domain of the antibody comprises the amino acid sequence of SEQ ID NO: 590. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 589, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 590. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 377, 378, 379, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 380, 381, 382.

[0148] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 591 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 592, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 591, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 592. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 591, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 592. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 383, 384, 385, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 386, 387, 388.

[0149] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 593 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 594, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 593, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 594. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 593, and the light chain variable domain of the antibody comprisesAttorney Docket No.: ELTH-011 / 01WO 336159-2069 the amino acid sequence of SEQ ID NO: 594. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 389, 390, 391, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 392, 393, 394.

[0150] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 595 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 596, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 595, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 596. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 595, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 596. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 395, 396, 397, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 398, 399, 400.

[0151] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 597 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 598, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 597, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 598. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 597, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 598. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 401, 402, 403, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 404, 405, 406.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0152] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 599 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 600, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 599, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 600. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 599, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 600. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 407, 408, 409, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 410, 411, 412.

[0153] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 601 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 602, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 601, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 602. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 601, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 602. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 413, 414, 415, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 416, 417, 418.

[0154] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 603 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 604, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 603, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 604. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 603, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 604. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 419, 420, 421, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 422, 423, 424.

[0155] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 605 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 606, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 605, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 606. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 605, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 606. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 425, 426, 427, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 428, 429, 430.

[0156] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 607 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 608, or an amino acid sequence with at least 80%, 81%, 82%, 83%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 607, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 608. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 607, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 608. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 431, 432, 433, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 434, 435, 436.

[0157] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 609 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 610, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 609, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 610. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 609, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 610. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 437, 438, 439, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 440, 441, 442.

[0158] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 611 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 612, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 611, and the light chain variableAttorney Docket No.: ELTH-011 / 01WO 336159-2069 domain of the antibody comprises the amino acid sequence of SEQ ID NO: 612. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 611, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 612. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 443, 444, 445, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 446, 447, 448.

[0159] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 613 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 614, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 613, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 614. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 613, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 614. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 449, 450, 451, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 452, 453, 454.

[0160] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 615 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 616, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 615, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 616. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 615, and the light chain variable domain of the antibody comprisesAttorney Docket No.: ELTH-011 / 01WO 336159-2069 the amino acid sequence of SEQ ID NO: 616. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 455, 456, 457, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 458, 459, 460.

[0161] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 617 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 618, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 617, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 618. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 617, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 618. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 461, 462, 463, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 464, 465, 466.

[0162] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 619 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 620, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 619, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 620. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 619, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 620. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 467, 468, 469, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 470, 471, 472.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0163] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 621 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 622, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 621, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 622. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 621, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 622. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 473, 474, 475, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 476, 477, 478.

[0164] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 623 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 624, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 623, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 623, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 624. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 479, 480, 481, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 482, 483, 484.

[0165] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 625 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 626, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 625, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 625, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 626. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 485, 486, 487, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 488, 489, 490.

[0166] In some embodiments, provided herein is a SIRPγ antibody, wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 627 or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 628, or an amino acid sequence with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 627, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 628. In some embodiments, the heavy chain variable domain of the antibody consists of the amino acid sequence of SEQ ID NO: 627, and the light chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 628. In some embodiments, the light chain variable domain comprises CDR sequences of SEQ ID NOS: 491, 492, 493, and the heavy chain variable domain comprises CDR sequences of SEQ ID NOS: 494, 495, 496.

[0167] By way of explanation, making reference to Tables 1 and 2, forty-seven (47) combinations of unique antibody sequences are provided (CDR sequences in Table 1; VH / VL sequences in Table 2). By way of example, and guidance to read the tables: Antibodies 1, 3, 4, 7, and 110 share the same combination of CDR sequences and also share the same combination of VH / VL sequences, but differ in some other aspect, e.g. may have different Fc regions. Likewise, it is noted that Antibodies 2, 5, 6, 8, and 111 share the same combinationAttorney Docket No.: ELTH-011 / 01WO 336159-2069 of CDR sequences and also share the same combination of VH / VL sequences but differ in some other aspect, e.g. may have different Fc regions.

[0168] Antibodies 1 and 2 comprise a rat IgG2b Fc.

[0169] Antibodies 3, 5, and 83-97 comprise a human IgG1 Fc of the disclosure.

[0170] Antibodies 4, 6, and 54-82 comprise a human IgG1 Fc of the disclosure comprising certain substitutions that lead to increased effector function, exhibiting increased affinity to Fc^R.

[0171] Antibodies 7 and 8 comprise a human IgG4 Fc of the disclosure comprising certain substitutions that lead to a decrease in the dynamic process of Fab-arm exchange, and further reduced effector function.

[0172] Antibodies 98-111 comprise a human IgG1 Fc of the disclosure comprising certain substitutions that lead to reduced effector function, leading to the silencing of the Fc (e.g. can comprise the LALA-PG substitutions). II. Treatment of EBV infection using SIRPγ antibodies

[0173] Provided herein are antibodies that recognize and bind to SIRP^, and have low or no affinity for binding SIRPα and SIRPβ. The antibodies disclosed herein may be used for the treatment of an EBV infection in a subject. In some embodiments, the subject is human. The subject can be of any age. e.g., infant, pediatric, adolescent, or adult (e.g. as per FDA guidelines). In some embodiments, the subject is treatment-naïve. In some embodiments, the subject has received one or more previous EBV treatments. In some embodiments, the subject is suffering from one or more EBV-associated diseases or disorders. In some embodiments, the subject is suffering from one or more additional comorbidities. These embodiments are discussed in further detail below. A. Epstein-Barr Virus (EBV) and Associated Disorders

[0174] In some embodiments, the EBV infection is an acute infection. In some embodiments, the EBV infection is a chronic infection. In some embodiments, the subject is infected with an EBV strain selected from the group consisting of type 1 (EBV-1), type 2 (EBV-2), and an EBV variant strain or subtype thereof. In some embodiments, the subject is infected with EBV-1. In some embodiments, the subject is infected with EBV-2. In some embodiments, the subject is infected with a variant or subtype strain of EBV-1 or EBV-2. In some embodiments, the subject is infected with multiple EBV strains.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0175] In some embodiment, the subject suffers from an EBV-associated disease or disorder. In some embodiments, the EBV-associated disease or disorder is selected from the group consisting of a secondary hemophagocytic lymphohistiocytosis (sHLH), cancer, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes (T1D), Macrophage activation syndrome (MAS), chronic NK lymphocytosis, and T cell chronic active EBV (CAEBV). In some embodiment, the cancer is a heme-based cancer. In some embodiment, the heme-based cancer is selected from the group consisting of lymphoma, leukemia, and myeloma. In some embodiment, the lymphoma is NK cell lymphoma, optionally nasal-type NK cell lymphoma. In some embodiment, the leukemia is NK cell leukemia. In some embodiments, treatment with a SIRPγ antibody of the disclosure prevents, delays, or mitigates of the onset of an EBV-associated disease or disorder.

[0176] In some embodiments, subject suffers from one or more additional comorbidities, associated with EBV infection. In some embodiments, the one or more additional comorbidities involves neurological symptoms. In some embodiments, the one or more additional comorbidities involves liver dysfunction neutropenia. B. Administration of Therapeutic SIRPγ antibodies

[0177] As contemplated herein, the SIRPγ antibodies of the present disclosure, and pharmaceutical compositions comprising the SIRPγ antibodies of the present disclosure are administered for EBV infection treatment in therapeutically effective amounts in at least one treatment phase. In some embodiments, the treatment phase is preceded by a priming dose phase. In some embodiments the subject is administered the antibody in one or more treatment phases. In some embodiments, the SIRPγ antibodies comprise the VH / VL amino acid sequence combinations of Table 2 or an amino acid sequence combination with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In exemplary embodiments, the SIRPγ antibodies comprise the CDR combinations of Table 1. In other embodiments, the SIRPγ antibodies of the disclosure comprise, 1, 2, 3, or 4 modifications to the CDR combinations of Table 1.

[0178] In some embodiments, the SIRPγ antibodies of the present disclosure are administered daily during the treatment phase where one or more treatment doses (or maintenance doses)Attorney Docket No.: ELTH-011 / 01WO 336159-2069 are administered. In some embodiments, the SIRPγ antibodies of the present disclosure are administered at least two times per week during the treatment phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered at least three times per week during the treatment phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered weekly during the treatment phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered every 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks during the treatment phase.

[0179] In some embodiments, the treatment phase lasts for a duration of at least 1 week. In some embodiments, the treatment phase lasts for a duration of at least 2 weeks. In some embodiments, the treatment phase lasts for a duration of at least 3 weeks. In some embodiments, the treatment phase lasts for a duration of at least 4 weeks. In some embodiments, the treatment phase lasts for a duration of at least 5 weeks. In some embodiments, the treatment phase lasts for a duration of at least 6 weeks. In some embodiments, the treatment phase lasts for a duration of at least 7 weeks. In some embodiments, the treatment phase lasts for a duration of at least 8 weeks. In some embodiments, the treatment phase lasts for a duration of at least 9 weeks. In some embodiments, the treatment phase lasts for a duration of at least 10 weeks. In some embodiments, the treatment phase lasts for a duration of at least 11 weeks. In some embodiments, the treatment phase lasts for a duration of at least 12 weeks. In some embodiments, the treatment phase lasts for a duration of at least 13 weeks. In some embodiments, the treatment phase lasts for a duration of at least 14 weeks. In some embodiments, the treatment phase lasts for a duration of at least 15 weeks. In some embodiments, the treatment phase lasts for a duration of at least 16 weeks. In some embodiments, the treatment phase lasts for a duration of at least 17 weeks. In some embodiments, the treatment phase lasts for a duration of at least 18 weeks. In some embodiments, the treatment phase lasts for a duration of at least 19 weeks. In some embodiments, the treatment phase lasts for a duration of at least 20 weeks. In some embodiments, the treatment phase lasts for a duration of at least 21 weeks. In some embodiments, the treatment phase lasts for a duration of at least 22 weeks. In some embodiments, the treatment phase lasts for a duration of at least 23 weeks. In some embodiments, the treatment phase lasts for a duration of at least 24 weeks. In some embodiments, the treatment phase lasts for a duration of 24 weeks or more. In some embodiments, the treatment phase lasts indefinitely, e.g. until symptoms or vial load haveAttorney Docket No.: ELTH-011 / 01WO 336159-2069 significantly decreased. In some embodiments, the treatment phase is terminated and recommenced at a later time.

[0180] The administration of the therapeutic SIRPγ antibodies during the treatment phase as described herein may be carried out intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, or through inhalation. Intravenous administration may be carried out via injection or infusion. In exemplary embodiments, the SIRPγ antibodies of the disclosure are administered intravenously. In other exemplary embodiments, the SIRPγ antibodies of the disclosure are administered subcutaneously. In yet other exemplary embodiments, the treatment phase comprises both intravenous and subcutaneous administration of the SIRPγ antibodies.

[0181] Administration of the therapeutic SIRPγ antibodies may be performed with any suitable pharmaceutically acceptable excipients, carriers, or other agents to provide suitable or improved tolerance, transfer, delivery, and the like.

[0182] In some embodiments the treatment phase comprises administering one or more doses of a SIRPγ antibody of the disclosure at a concentration of at least about 0.01 mg / kg, of at least about 0.03 mg / kg, of at least about 0.05 mg / kg, of at least about 0.1 mg / kg, of at least about 0.3 mg / kg, of at least about 0.5 mg / kg, of at least about 1.0 mg / kg, of at least about 3.0 mg / kg, of at least 5.0 mg / kg, of at least about 10 mg / kg per dose, of at least about 20 mg / kg per dose, of at least about 30 mg / kg per dose, of at least about 40 mg / kg per dose, of at least about 50 mg / kg per dose, of at least about 60 mg / kg per dose, of at least about 70 mg / kg per dose, of at least about 80 mg / kg per dose, of at least about 90 mg / kg per dose, of at least about 100 mg / kg per dose. In some embodiments the treatment phase comprises administering one or more doses of a SIRPγ antibody of the disclosure at a concentration of about 0.01 mg / kg to about 0.03 mg / kg, of about 0.03 mg / kg to about 0.05 mg / kg, of about 0.05 mg / kg to about 0.1 mg / kg, of about 0.1 mg / kg to about 0.3 mg / kg, of about 0.3 mg / kg to about 0.5 mg / kg, of about 0.5 mg / kg to about 1.0 mg / kg, of about 1.0 mg / kg to about 3.0 mg / kg, of about 3.0 mg / kg to about 5.0 mg / kg, of about 5.0 mg / kg to about 10 mg / kg, of about 0.1 mg / kg to about 1 mg / kg, of about 0.3 mg / kg to about 3 mg / kg, of about 0.5 mg / kg to about 0.5 mg / kg, of about 0.5 mg / kg to about 5 mg / kg, of about 0.1 mg / kg to about 0.3 mg / kg, of about 0.01 mg / kg to about 0.05 mg / kg, of about 0.01 mg / kg to about 0.3 mg / kg, of about 0.03 mg / kg to about 0.1 mg / kg, of about 0.03 mg / kg to about 0.3 mg / kg, of about 0.05Attorney Docket No.: ELTH-011 / 01WO 336159-2069 mg / kg to about 0.5 mg / kg, of about 0.05 mg / kg to about 0.3 mg / kg, of about 0.05 mg / kg to about 3 mg / kg, of about 0.05 mg / kg to about 5 mg / kg, of about 0.1 mg / kg to about 3 mg / kg, 0.1 mg / kg to about 5 mg / kg, 0.3 mg / kg to about 1 mg / kg, 0.3 mg / kg to about 3 mg / kg, 0.3 mg / kg to about 5 mg / kg, about 3.0 mg / kg to about 10 mg / kg, about 10mg / kg to about 20mg / kg, about 20mg / kg to about 30mg / kg, about 30mg / kg to about 40mg / kg, about 40mg / kg to about 50mg / kg, about 50mg / kg to about 60mg / kg, about 60mg / kg to about 70mg / kg, about 70mg / kg to about 80mg / kg, about 80mg / kg to about 90mg / kg, or about 90mg / kg to about 100mg / kg. In exemplary embodiments, the route of administration is intravenous or subcutaneous.

[0183] As noted above, in some embodiments the subject is administered one or more priming doses during the one or more priming dose phases prior to the one or more treatment phases. Without being held to theory or mechanism, the priming dose may sever several roles, e.g., may reduce infusion reaction severity, improve the responsiveness of the subject during the treatment phase and / or allow for the target concentration of the antibody treatment to be achieved rapidly.

[0184] In some embodiments, the SIRPγ antibodies of the present disclosure are administered for a period of 1 day during the priming dose phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered daily for a period of 2 days or at least 2 days during the priming dose phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered daily for a period of 3 days, or at least 3 days during the priming dose phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered daily for a period of 4 days, or at least 4 days during the priming dose phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered daily for a period of 5 days, or at least 5 days during the priming dose phase. In some embodiments, the SIRPγ antibodies of the present disclosure are administered daily for a period of more than 5 days during the priming dose phase.

[0185] In some embodiments, one or more additional priming dose phases may be administered after the first treatment phase is terminated and before a subsequent treatment phase is recommenced.

[0186] The administration of the therapeutic SIRPγ antibodies during the priming dose phase as described herein may be carried out intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally,Attorney Docket No.: ELTH-011 / 01WO 336159-2069 intraventricularly, intranasally, transmucosally, through implantation, or through inhalation. Intravenous administration during the priming dose phase may be carried out via injection or infusion. In exemplary embodiments, the SIRPγ antibodies of the disclosure are administered intravenously during the priming dose phase. In exemplary embodiments, the SIRPγ antibodies of the disclosure are administered subcutaneously during the priming dose phase. In exemplary embodiments the SIRPγ antibodies of the disclosure are administered subcutaneously and intravenously during the priming dose phase. Administration of the therapeutic SIRPγ antibodies during the priming dose phase may be performed with any suitable excipients, carriers, or other agents to provide suitable or improved tolerance, transfer, delivery, and the like.

[0187] In some embodiments the priming dose phase comprises administering one or more doses of a SIRPγ antibody of the disclosure at a concentration of about 0.01 mg / kg, of about 0.03 mg / kg, of about 0.05 mg / kg, of about 0.1 mg / kg, of about 0.3 mg / kg, of about 0.5 mg / kg, of about 1.0 mg / kg, of about 3.0 mg / kg, or of about 5.0 mg / kg per dose. In some embodiments the treatment phase comprises administering one or more doses of a SIRPγ antibody of the disclosure at a concentration of at least about 0.01 mg / kg, of at least about 0.03 mg / kg, of at least about 0.05 mg / kg, of at least about 0.1 mg / kg, of at least about 0.3 mg / kg, of at least about 0.5 mg / kg, of at least about 1.0 mg / kg, of at least about 3.0 mg / kg, of at least 5.0 mg / kg or of at least about 10 mg / kg per dose. In some embodiments the treatment phase comprises administering one or more doses of a SIRPγ antibody of the disclosure at a concentration of about 0.01 mg / kg to about 0.03 mg / kg, of about 0.03 mg / kg to about 0.05 mg / kg, of about 0.05 mg / kg to about 0.1 mg / kg, of about 0.1 mg / kg to about 0.3 mg / kg, of about 0.3 mg / kg to about 0.5 mg / kg, of about 0.5 mg / kg to about 1.0 mg / kg, of about 1.0 mg / kg to about 3.0 mg / kg, of about 3.0 mg / kg to about 5.0 mg / kg, of about 5.0 mg / kg to about 10 mg / kg, of about 0.1 mg / kg to about 1 mg / kg, of about 0.3 mg / kg to about 3 mg / kg, of about 0.5 mg / kg to about 0.5 mg / kg, of about 0.5 mg / kg to about 5 mg / kg, of about 0.1 mg / kg to about 0.3 mg / kg, of about 0.01 mg / kg to about 0.05 mg / kg, of about 0.01 mg / kg to about 0.3 mg / kg, of about 0.03 mg / kg to about 0.1 mg / kg, of about 0.03 mg / kg to about 0.3 mg / kg, of about 0.05 mg / kg to about 0.5 mg / kg, of about 0.05 mg / kg to about 0.3 mg / kg, of about 0.05 mg / kg to about 3 mg / kg, of about 0.05 mg / kg to about 5 mg / kg, of about 0.1 mg / kg to about 3 mg / kg, 0.1 mg / kg to about 5 mg / kg, 0.3 mg / kg to about 1 mg / kg, 0.3 mg / kg to about 3 mg / kg, 0.3 mg / kg to about 5 mg / kg, or about 3.0 mg / kg to about 10 mg / kg. In exemplary embodiments, the route of administration is intravenous or subcutaneous.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 C. Pharmaceutical Compositions

[0188] The disclosure also provides pharmaceutical compositions comprising any one of the SIRPγ antibodies disclosed herein, and optionally a pharmaceutical acceptable excipient or carrier. In some embodiments, the pharmaceutical composition is sterile. The pharmaceutical compositions may be formulated to be compatible with their intended routes of administration. In some embodiments, the pharmaceutical compositions of the disclosure are suitable for administration to a human subject. D. Combination Therapies

[0189] The administration of any one of the therapeutic SIRPγ antibodies provided herein may be in combination with any other known drugs or treatments for diseases or conditions. In some embodiments, the disease or condition is associated with overactivation and / or hyperproliferation of myeloid cells, lymphocytes, or other cells expressing SIRPγ. In some embodiments, the disease or condition is an autoimmune disease or condition. In some embodiments, the disease or condition is a neoplastic disorder or malignancy.

[0190] In some embodiments, a therapeutic SIRPγ antibody may be used in combination with corticosteroids (e.g. – dexamethasone).

[0191] In some embodiments, a therapeutic SIRPγ antibody provided herein, is used in combination with one or more additional therapeutic or investigational agents is selected from the group consisting of: a chemotherapeutic agent, an immunotherapeutic agent, a CAR T therapeutic agent, a JAK inhibitor, a radiotherapeutic agent, methotrexate, azathioprine, dexamethasone, a biological therapeutic agent, a TNF inhibitor, anakinra, antimicrobials, etoposide, tocilizumab, emapalumab, alemtuzumab, cyclosporin, intravenous immunoglobulin (IVIG), rituximab, other corticosteroids, any combination chemotherapy regimens, antiviral agents (e.g., nucleoside analogues), interleukin-2, interferon alfa, intravenous immunoglobulins, and etoposide.

[0192] In some embodiments, one or more therapeutic agents are administered as a premedication therapy. In some embodiments, the therapeutic agent used as a premedication therapy is one or more of dexamethasone, etoposide, emapalumab, and CHOEP chemotherapy.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 E. Evaluation of SIRPγ antibody Therapy

[0193] In some embodiments, a predicted prognosis and / or likelihood of response to treatment is obtained by evaluating EBV viral load.

[0194] In some embodiments, response to treatment is monitored by improvement in signs and symptoms of EBV infection, such as fever, fatigue, anorexia, headache, neurological symptoms, confusion, depression, abdominal pain, spleen abnormalities, liver abnormalities, skin changes, pain, myalgias, bone pain, and general wellbeing.

[0195] In some embodiments, a predicted prognosis and / or likelihood of response to treatment is obtained by evaluating a ratio of sCD25 / ferritin.

[0196] In some embodiments, a predicted prognosis and / or likelihood of response to treatment is obtained by measuring circulating monocyte and lymphocyte counts.

[0197] In some embodiments, evaluation of the SIRPγ antibody therapy in a subject is comprised of measuring or monitoring one or more biomarkers from a biological sample obtained from the subject which may include EBV viral load, ferritin, sCD25, sCD25 / ferritin ratio, C-reactive protein (CRP), fibrinogen, CXCL9, CXCL10, sCD163, LDH, IFN-gamma, IL-6, TNF-alpha, IL-8, IL-10, IL-18, GDF-15, IL-1RA, MDC, ST2, Alanine aminotransferase (ALT), and IL-16. In some embodiments, evaluation of the SIRPγ antibody therapy in a subject is comprised of monitoring positron emission tomography (PET)- SCANs.

[0198] In some embodiments, treatment with a SIRPγ antibody of the disclosure reduces the EBV viral load in the subject. In some embodiments, the viral load is reduced in the hematopoietic system (bone marrow or blood cells including stem and progenitor cells). In some embodiments, the viral load is reduced in the blood. In some embodiments, the viral load is reduced in the bone marrow. In some embodiments, the viral load is reduced in B cells, T cells, or myeloid cells. In some embodiments, the EBV viral load is reduced at least by 5% to 100%. In some embodiments, the EBV viral load is reduced at least by 5% to about 10%. In some embodiments, the EBV viral load is reduced at least by 10% to about 20%. In some embodiments, the EBV viral load is reduced at least by 20% to about 30%. In some embodiments, the EBV viral load is reduced at least by 30% to about 40%. In some embodiments, the EBV viral load is reduced at least by 40% to about 50%. In some embodiments, the EBV viral load is reduced at least by 50% to about 60%. In some embodiments, the EBV viral load is reduced at least by 60% to about 70%. In some embodiments, the EBV viral load is reduced at least by 70% to about 80%. In someAttorney Docket No.: ELTH-011 / 01WO 336159-2069 embodiments, the EBV viral load is reduced at least by 80% to about 90%. In some embodiments, the EBV viral load is reduced at least by 90% to about 100%.

[0199] In some embodiments, treatment with a SIRPγ antibody of the disclosure results in the depletion of SIRPγ expressing cells. In some embodiments, the SIRPγ expressing cells are T cells. III. Exemplary Enumerated Embodiments

[0200] The following non-limiting enumerated embodiments are provided as exemplary.

[0201] Embodiment I-1. A method of treating an Epstein-Barr virus (EBV) infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a SIRP^ binding antibody, wherein the SIRP^ binding antibody is specific for SIRP^, and wherein the antibody has low or no affinity for binding SIRPα and SIRPβ.

[0202] Embodiment I-2. The method of Embodiment I-1, wherein the antibody is a monoclonal antibody.

[0203] Embodiment I-3. The method of Embodiment I-1, wherein the antibody is an antibody fragment.

[0204] Embodiment I-4. The method of Embodiment I-1, wherein the antibody is a human antibody.

[0205] Embodiment I-5. The method of Embodiment I-1, wherein the antibody is a humanized antibody.

[0206] Embodiment I-6. The method of Embodiment I-1, wherein the antibody is a chimeric antibody.

[0207] Embodiment I-7. The method of Embodiment I-1, wherein the antibody is a full- length antibody.

[0208] Embodiment I-8. The method of Embodiment I-1, wherein the antibody is bispecific for an additional target.

[0209] Embodiment I-9. The method of any one of Embodiment I-1-Embodiment I-8, wherein the EBV infection is acute or chronic.

[0210] Embodiment I-10. The method of any one of Embodiment I-1-Embodiment I-9, wherein the subject is infected with an EBV strain selected from the group consisting of type 1 (EBV-1), type 2 (EBV-2), and an EBV variant strain or subtype thereof.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0211] Embodiment I-11. The method of any one of Embodiment I-1-Embodiment I-10, wherein the subject suffers from an EBV-associated disease or disorder.

[0212] Embodiment I-12. The method of any one of Embodiment I-1-Embodiment I-10, wherein the treatment prevents, delays, or mitigates of the onset of an EBV-associated disease or disorder.

[0213] Embodiment I-13. The method of Embodiment I-11 or Embodiment I-12, wherein the EBV-associated disease or disorder is selected from the group consisting of a secondary hemophagocytic lymphohistiocytosis (sHLH), cancer, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes (T1D), Macrophage activation syndrome (MAS), chronic NK lymphocytosis, and T cell chronic active EBV (CAEBV).

[0214] Embodiment I-14. The method of Embodiment I-13, wherein the cancer is a heme-based cancer.

[0215] Embodiment I-15. The method of Embodiment I-14, wherein the heme-based cancer is selected from the group consisting of lymphoma, leukemia, and myeloma.

[0216] Embodiment I-16. The method of Embodiment I-15, wherein the lymphoma is NK cell lymphoma, optionally nasal-type NK cell lymphoma.

[0217] Embodiment I-17. The method of Embodiment I-15, wherein the leukemia is NK cell leukemia.

[0218] Embodiment I-18. The method of any one of Embodiment I-1-Embodiment I-17, wherein the subject suffers from one or more additional comorbidities.

[0219] Embodiment I-19. The method of any one of Embodiment I-1-Embodiment I-18, wherein the treatment reduces the EBV viral load in the subject.

[0220] Embodiment I-20. The method of Embodiment I-19, wherein the EBV viral load is reduced at least by 10%.

[0221] Embodiment I-21. The method of Embodiment I-20, wherein the EBV viral load is reduced in the blood.

[0222] Embodiment I-22. The method of Embodiment I-20, wherein the EBV viral load is reduced in B cells, T cells, NK cells, or myeloid cells.

[0223] Embodiment I-23. The method of Embodiment I-20, wherein the EBV viral load is reduced in bone marrow.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0224] Embodiment I-24. The method of any one of Embodiment I-1-Embodiment I-23, wherein the treatment results in the depletion of SIRPγ-expressing cells.

[0225] Embodiment I-25. The method of Embodiment I-24, wherein the SIRPγ- expressing cells are B cells, T cells, or NK cells.

[0226] Embodiment I-26. The method of any one of Embodiment I-1-Embodiment I-25, wherein the method comprises monitoring EBV viral load, PET-SCANs, C-reactive protein (CRP), sCD25, and / or ferritin peak, minimum, maximum, and reduction prospectively to diagnose and predict prognosis, and / or likelihood of response to therapy for the EBV infection, EBV associated disease or disorder, and / or the one or more additional comorbidities.

[0227] Embodiment I-27. The method of any one of Embodiment I-1-Embodiment I-26, wherein the SIRPγ binding antibody is administered to the subject subcutaneously or intravenously.

[0228] Embodiment I-28. The method of any one of Embodiment I-1-Embodiment I-27, wherein the administration occurs in a treatment phase.

[0229] Embodiment I-29. The method of Embodiment I-28, wherein the method comprises more than one treatment phase.

[0230] Embodiment I-30. The method of any one of of Embodiment I-1-Embodiment I- 29, wherein the treatment phase comprises a dose of at least about 0.01 mg / kg to about 5.0 mg / kg of the SIRPγ binding antibody.

[0231] Embodiment I-31. The method of any Embodiment I-30, wherein the treatment phase comprises a dose about 0.1 mg / kg to about 1.0 mg / kg of the SIRPγ binding antibody.

[0232] Embodiment I-32. The method of any one of Embodiment I-1-Embodiment I-31, wherein the SIRPγ binding antibody is administered in combination with an additional therapy.

[0233] Embodiment I-33. The method of Embodiment I-32, wherein the additional therapy is selected from the group consisting of corticosteroids, antiviral agents (e.g., nucleoside analogues), interleukin-2, interferon alfa, intravenous immunoglobulins, etoposide, and other chemotherapy agents.

[0234] Embodiment I-34. The method of any one of Embodiment I-1-Embodiment I-33, wherein the SIRPγ binding antibody is administered in a pharmaceutical composition, wherein the pharmaceutical composition comprises the antibody, and a pharmaceutically acceptable carrier.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0235] Embodiment I-35. The method of any one of Embodiment I-1-Embodiment I-34, wherein the antibody comprises a complementarity determining region (CDR) sequence combination selected from the group consisting of: a. SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220; b. SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226; c. SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232; d. SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238; e. SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244; f. SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250; g. SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256; h. SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262; i. SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268; j. SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 271, SEQ ID NO: 272, SEQ ID NO: 273, SEQ ID NO: 274; k. SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, SEQ ID NO: 278, SEQ ID NO: 279, SEQ ID NO: 280; l. SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286; m. SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292; n. SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298; o. SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 p. SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310; q. SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316; r. SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322; s. SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328; t. SEQ ID NO: 329, SEQ ID NO: 330, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334; u. SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340; v. SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 343, SEQ ID NO: 344, SEQ ID NO: 345, SEQ ID NO: 346; w. SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 350, SEQ ID NO: 351, SEQ ID NO: 352; x. SEQ ID NO: 353, SEQ ID NO: 354, SEQ ID NO: 355, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 358; y. SEQ ID NO: 359, SEQ ID NO: 360, SEQ ID NO: 361, SEQ ID NO: 362, SEQ ID NO: 363, SEQ ID NO: 364; z. SEQ ID NO: 365, SEQ ID NO: 366, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 369, SEQ ID NO: 370; aa. SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 373, SEQ ID NO: 374, SEQ ID NO: 375, SEQ ID NO: 376; bb. SEQ ID NO: 377, SEQ ID NO: 378, SEQ ID NO: 379, SEQ ID NO: 380, SEQ ID NO: 381, SEQ ID NO: 382; cc. SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388; dd. SEQ ID NO: 389, SEQ ID NO: 390, SEQ ID NO: 391, SEQ ID NO: 392, SEQ ID NO: 393, SEQ ID NO: 394; ee. SEQ ID NO: 395, SEQ ID NO: 396, SEQ ID NO: 397, SEQ ID NO: 398, SEQ ID NO: 399, SEQ ID NO: 400;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 ff. SEQ ID NO: 401, SEQ ID NO: 402, SEQ ID NO: 403, SEQ ID NO: 404, SEQ ID NO: 405, SEQ ID NO: 406; gg. SEQ ID NO: 407, SEQ ID NO: 408, SEQ ID NO: 409, SEQ ID NO: 410, SEQ ID NO: 411, SEQ ID NO: 412; hh. SEQ ID NO: 413, SEQ ID NO: 414, SEQ ID NO: 415, SEQ ID NO: 416, SEQ ID NO: 417, SEQ ID NO: 418; ii. SEQ ID NO: 419, SEQ ID NO: 420, SEQ ID NO: 421, SEQ ID NO: 422, SEQ ID NO: 423, SEQ ID NO: 424; jj. SEQ ID NO: 425, SEQ ID NO: 426, SEQ ID NO: 427, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430; kk. SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436; ll. SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, SEQ ID NO: 441, SEQ ID NO: 442; mm. SEQ ID NO: 443, SEQ ID NO: 444, SEQ ID NO: 445, SEQ ID NO: 446, SEQ ID NO: 447, SEQ ID NO: 448; nn. SEQ ID NO: 449, SEQ ID NO: 450, SEQ ID NO: 451, SEQ ID NO: 452, SEQ ID NO: 453, SEQ ID NO: 454; oo. SEQ ID NO: 455, SEQ ID NO: 456, SEQ ID NO: 457, SEQ ID NO: 458, SEQ ID NO: 459, SEQ ID NO: 460; pp. SEQ ID NO: 461, SEQ ID NO: 462, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466; qq. SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 470, SEQ ID NO: 471, SEQ ID NO: 472; rr. SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478; ss. SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484; tt. SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490; and uu. SEQ ID NO: 491, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, SEQ ID NO: 495, SEQ ID NO: 496.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0236] Embodiment I-36. The method of any one of Embodiment I-1-Embodiment I-35, wherein the SIRPγ binding antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein a. the VH comprises the amino acid sequence of SEQ ID NO: 535, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 536, or an amino acid sequence with at least 80% sequence identity thereto; b. the VH comprises the amino acid sequence of SEQ ID NO: 537, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 538, or an amino acid sequence with at least 80% sequence identity thereto; c. the VH comprises the amino acid sequence of SEQ ID NO: 539, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 540, or an amino acid sequence with at least 80% sequence identity thereto; d. the VH comprises the amino acid sequence of SEQ ID NO: 541, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 542, or an amino acid sequence with at least 80% sequence identity thereto; e. the VH comprises the amino acid sequence of SEQ ID NO: 543, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 544, or an amino acid sequence with at least 80% sequence identity thereto; f. the VH comprises the amino acid sequence of SEQ ID NO: 545, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 546, or an amino acid sequence with at least 80% sequence identity thereto; g. the VH comprises the amino acid sequence of SEQ ID NO: 547, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 548, or an amino acid sequence with at least 80% sequence identity thereto; h. the VH comprises the amino acid sequence of SEQ ID NO: 549, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 amino acid sequence of SEQ ID NO: 550, or an amino acid sequence with at least 80% sequence identity thereto; i. the VH comprises the amino acid sequence of SEQ ID NO: 551, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 552, or an amino acid sequence with at least 80% sequence identity thereto; j. the VH comprises the amino acid sequence of SEQ ID NO: 553, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 554, or an amino acid sequence with at least 80% sequence identity thereto; k. the VH comprises the amino acid sequence of SEQ ID NO: 555, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 556, or an amino acid sequence with at least 80% sequence identity thereto; l. the VH comprises the amino acid sequence of SEQ ID NO: 557, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 558, or an amino acid sequence with at least 80% sequence identity thereto; m. the VH comprises the amino acid sequence of SEQ ID NO: 559, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 560, or an amino acid sequence with at least 80% sequence identity thereto; n. the VH comprises the amino acid sequence of SEQ ID NO: 561, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 562, or an amino acid sequence with at least 80% sequence identity thereto; o. the VH comprises the amino acid sequence of SEQ ID NO: 563, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 564, or an amino acid sequence with at least 80% sequence identity thereto; p. the VH comprises the amino acid sequence of SEQ ID NO: 565, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 amino acid sequence of SEQ ID NO: 566, or an amino acid sequence with at least 80% sequence identity thereto; q. the VH comprises the amino acid sequence of SEQ ID NO: 567, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 568, or an amino acid sequence with at least 80% sequence identity thereto; r. the VH comprises the amino acid sequence of SEQ ID NO: 569, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 570, or an amino acid sequence with at least 80% sequence identity thereto; s. the VH comprises the amino acid sequence of SEQ ID NO: 571, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 572, or an amino acid sequence with at least 80% sequence identity thereto; t. the VH comprises the amino acid sequence of SEQ ID NO: 573, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 574, or an amino acid sequence with at least 80% sequence identity thereto; u. the VH comprises the amino acid sequence of SEQ ID NO: 575, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 576, or an amino acid sequence with at least 80% sequence identity thereto; v. the VH comprises the amino acid sequence of SEQ ID NO: 577, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 578, or an amino acid sequence with at least 80% sequence identity thereto; w. the VH comprises the amino acid sequence of SEQ ID NO: 579, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 580, or an amino acid sequence with at least 80% sequence identity thereto; x. the VH comprises the amino acid sequence of SEQ ID NO: 581, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 amino acid sequence of SEQ ID NO: 582, or an amino acid sequence with at least 80% sequence identity thereto; y. the VH comprises the amino acid sequence of SEQ ID NO: 583, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 584, or an amino acid sequence with at least 80% sequence identity thereto; z. the VH comprises the amino acid sequence of SEQ ID NO: 585, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 586, or an amino acid sequence with at least 80% sequence identity thereto; aa. the VH comprises the amino acid sequence of SEQ ID NO: 587, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 588, or an amino acid sequence with at least 80% sequence identity thereto; bb. the VH comprises the amino acid sequence of SEQ ID NO: 589, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 590, or an amino acid sequence with at least 80% sequence identity thereto; cc. the VH comprises the amino acid sequence of SEQ ID NO: 591, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 592, or an amino acid sequence with at least 80% sequence identity thereto; dd. the VH comprises the amino acid sequence of SEQ ID NO: 593, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 594, or an amino acid sequence with at least 80% sequence identity thereto; ee. the VH comprises the amino acid sequence of SEQ ID NO: 595, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 596, or an amino acid sequence with at least 80% sequence identity thereto; ff. the VH comprises the amino acid sequence of SEQ ID NO: 597, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 amino acid sequence of SEQ ID NO: 598, or an amino acid sequence with at least 80% sequence identity thereto; gg. the VH comprises the amino acid sequence of SEQ ID NO: 599, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 600, or an amino acid sequence with at least 80% sequence identity thereto; hh. the VH comprises the amino acid sequence of SEQ ID NO: 601, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 602, or an amino acid sequence with at least 80% sequence identity thereto; ii. the VH comprises the amino acid sequence of SEQ ID NO: 603, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 604, or an amino acid sequence with at least 80% sequence identity thereto; jj. the VH comprises the amino acid sequence of SEQ ID NO: 605, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 606, or an amino acid sequence with at least 80% sequence identity thereto; kk. the VH comprises the amino acid sequence of SEQ ID NO: 607, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 608, or an amino acid sequence with at least 80% sequence identity thereto; ll. the VH comprises the amino acid sequence of SEQ ID NO: 609, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 610, or an amino acid sequence with at least 80% sequence identity thereto; mm. the VH comprises the amino acid sequence of SEQ ID NO: 611, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 612, or an amino acid sequence with at least 80% sequence identity thereto; nn. the VH comprises the amino acid sequence of SEQ ID NO: 613, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises theAttorney Docket No.: ELTH-011 / 01WO 336159-2069 amino acid sequence of SEQ ID NO: 614, or an amino acid sequence with at least 80% sequence identity thereto; oo. the VH comprises the amino acid sequence of SEQ ID NO: 615, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 616, or an amino acid sequence with at least 80% sequence identity thereto; pp. the VH comprises the amino acid sequence of SEQ ID NO: 617, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 618, or an amino acid sequence with at least 80% sequence identity thereto; qq. the VH comprises the amino acid sequence of SEQ ID NO: 619, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 620, or an amino acid sequence with at least 80% sequence identity thereto; rr. the VH comprises the amino acid sequence of SEQ ID NO: 621, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 622, or an amino acid sequence with at least 80% sequence identity thereto; ss. the VH comprises the amino acid sequence of SEQ ID NO: 623, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 624, or an amino acid sequence with at least 80% sequence identity thereto; tt. the VH comprises the amino acid sequence of SEQ ID NO: 625, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 626, or an amino acid sequence with at least 80% sequence identity thereto; and uu. the VH comprises the amino acid sequence of SEQ ID NO: 627, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 628, or an amino acid sequence with at least 80% sequence identity thereto.

[0237] Embodiment I-37. The method of any one of Embodiment I-1-Embodiment I-36, wherein the SIRPγ binding antibody comprises an Fc domain.Attorney Docket No.: ELTH-011 / 01WO 336159-2069

[0238] Embodiment I-38. The method of Embodiment I-37, wherein the Fc domain is selected from the group consisting of human IgG1, IgG2, IgG3, and IgG4.

[0239] Embodiment I-39. The method of Embodiment I-38, wherein the Fc domain is from the heavy chain IgG amino acid sequences of any one of SEQ ID NOS: 15-46.

[0240] Embodiment I-40. The method of Embodiment I-39, wherein the heavy chain Fc domain comprises one or more amino acid substitutions relative to SEQ ID NO: 15 or SEQ ID NO: 39 at a position selected from the group consisting of: 215, 221, 222, 228, 234, 235, 236, 239, 240, 241, 243, 244, 245, 247, 250, 252, 254, 256, 262, 263, 264, 265, 266, 267, 268, 269, 270, 292, 296, 297, 298, 299, 300, 305, 313, 324, 325, 326, 327, 328, 329, 330, 332, 333, 334, 345, 396, 428, 430, 433, 434, and 440 wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0241] Embodiment I-41. Use of a SIRP^ binding antibody for the treatment of an Epstein-Barr virus (EBV) infection in a subject in need thereof, wherein the SIRP^ binding antibody is specific for SIRP^, and wherein the antibody has low or no affinity for binding SIRPα and SIRPβ.

[0242] Embodiment I-42. Use of a SIRP^ binding antibody for the manufacture of a medicament for the treatment of an Epstein-Barr virus (EBV) infection in a subject in need thereof, wherein the SIRP^ binding antibody is specific for SIRP^, and wherein the antibody has low or no affinity for binding SIRPα and SIRPβ.

[0243] Embodiment I-43. A method of treating an Epstein-Barr virus (EBV) infection in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-SIRP^ antibody, wherein the antibody comprises a means for binding human SIRPγ but not SIRPα or SIRPβ.

[0244] The following Examples are merely illustrative and are not meant to limit any aspects of the present disclosure in any way.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 EXAMPLES Example 1: Reduction of Viral Load after SIRPα / β / γ binding Antibody Treatment

[0245] The following examples describes clinical efficacy signals in EBV-infected patients. Patient 602-01 has EBV-triggered sHLH; patients 601-10 and 609-02 have EBV-triggered sHLH in the setting of a malignancy. As these patients were not receiving chemotherapy or had residual effects of chemotherapy at the time of the key events described, these patients provide valuable opportunities to better assess SIRPα / β / γ binding antibody effects on response and PD markers for EBV infection and sHLH, not confounded by chemotherapy. All patients entered the study sHLH treatment naïve. A monoclonal SIRPα / β / γ specific antibody, herein referred to as “SIRP1” was assessed. The CDR, VH, and VL amino acid sequences for SIRP1 can be found in U.S. Patent No.12,187,797 (identified therein as Antibody 28), the sequences of which are hereby expressly incorporated by reference for the purpose of provide support for the structure of SIRP1.

[0246] Dose administrations occurred as priming doses or maintenance doses (Table E1). The dose regimen, including the priming doses to reduce infusion reactions. Table E1: Dose Regimen

[0247] Participants received dexamethasone as background therapy (initially 10 mg / m2) and premedication. After Day 15, a dexamethasone tapering regimen may be considered upon HLH disease control to the minimum effective dose to prevent infusion reactions (typically 4- 8 mg of dexamethasone, however, some patients did not receive any dexamethasone premedication).

[0248] Patient 602-01 with EBV-triggered sHLH presenting with neutropenia, neurological symptoms and liver dysfunction. Patient received background dexamethasone with SIRP1. There was rapid improvement of HLH markers and symptoms (FIG.1B). The PD effects were noted on monocytes and lymphocytes. Upon improvement of HLH activity, there was aAttorney Docket No.: ELTH-011 / 01WO 336159-2069 recovery of blood counts (healthy blood cells). Patient completed 12-week course of treatment.

[0249] Patient 601-10 with Peripheral T-Cell Lymphoma (PTCL)-triggered HLH. Patient had an initial response to SIRP1 with background dexamethasone and CHOEP chemotherapy. There was an acute rise in HLH activity (e.g., ferritin and ALT) beginning on Day 38 (FIG. 2). Work-up identified that this was triggered by a concurrent acute EBV infection (bone marrow viral load ~3.9 million IU / mL). The antibody dosing had been interrupted twice for unrelated adverse effects. Without any added therapies for the HLH or for the PTCL, the patient restarted SIRP1 at maintenance dosing, twice weekly and there was rapid control of HLH activity and reduction of EBV viral load. The investigator could not attribute the rapid resolution of HLH activity to any added therapies or lingering chemotherapy effects.

[0250] Patient 609-02 with EBV+ diffuse large B-cell lymphoma (DLBCL). The patient developed a brisk onset of HLH secondary to lymphoma progression and EBV presence in the blood. Ferritin was 8,791 ng / mL with sIL2R >80,000 pg / mL, fibrinogen of 104 mg / dL, TG of 326 mg / dL, and with progressive pancytopenia and splenomegaly (FIG.3). Other than background dexamethasone, at 20 mg on Day 1, there was no additional HLH-directed or cancer-directed therapies including chemotherapy through Day 11. The biomarker responses summarized in Figure 2, especially sCD25 and CRP can be attributed to SIRP1 which includes a reduction of blood EBV viral load on day 11. Example 2: SIRP Expression on B Cells from EBV triggered sHLH Patient

[0251] Patient US603-EAP001 was a 15-year-old female with EBV-triggered sHLH. Patient was previously treated with etoposide and with emapalumab twice weekly. Patient had completed the priming regimen but her first weekly dose of SIRP1 was held due to increased platelet transfusion requirement for menstrual bleeding (in addition to ongoing mucosal and GI bleeding), progressive EBV infection, and progressive sHLH. Because study drug had been held, Patient was required to restart the priming regimen and received 0.1 mg / kg. In total Patient received 5 infusions of SIRP1 (cumulative dose of 1.1 mg / kg). However, prior to resumption of SIRP1, Patient’s clinical condition worsened. Patient had a fever followed by persistent hypotension, and became too critically ill to receive more SIRP1 and died due to bacterial sepsis, likely from a GI source as been the patient’s prior sepsis episodes. A pre- SIRP1 treatment blood sample was sent for flow analysis of SIRP expression. A second SIRPα / β / γ specific antibody, “SIRP2” (modified to have no Fc effector function) was used toAttorney Docket No.: ELTH-011 / 01WO 336159-2069 identify SIRP expression. The data showed that >90% of the patient’s B-cells had high expression of SIRP compared with normal healthy controls (FIG.4A-B). The CDR, VH, and VL amino acid sequences for SIRP2 can be found in U.S. Patent No.12,187,797 (identified therein as Antibody 24), the sequences of which are hereby expressly incorporated by reference for the purpose of provide support for the structure of SIRP2. This is the first example of B-cells overexpressing SIRPs in the setting of EBV infection, which suggests SIRP as a therapeutic target for the treatment of EBV infection.

Claims

Attorney Docket No.: ELTH-011 / 01WO 336159-2069 CLAIMS 1. A method of treating an Epstein-Barr virus (EBV) infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a SIRP^ binding antibody, wherein the SIRP^ binding antibody is specific for SIRP^, and wherein the antibody has low or no affinity for binding SIRPα and SIRPβ.

2. The method of claim 1, wherein the antibody is a monoclonal antibody.

3. The method of claim 1, wherein the antibody is an antibody fragment.

4. The method of claim 1, wherein the antibody is a human antibody.

5. The method of claim 1, wherein the antibody is a humanized antibody.

6. The method of claim 1, wherein the antibody is a chimeric antibody.

7. The method of claim 1, wherein the antibody is a full-length antibody.

8. The method of claim 1, wherein the antibody is bispecific for an additional target.

9. The method of any one of claims 1-8, wherein the EBV infection is acute or chronic.

10. The method of any one of claims 1-9, wherein the subject is infected with an EBV strain selected from the group consisting of type 1 (EBV-1), type 2 (EBV-2), and an EBV variant strain or subtype thereof.

11. The method of any one of claims 1-10, wherein the subject suffers from an EBV- associated disease or disorder.

12. The method of any one of claims 1-10, wherein the treatment prevents, delays, or mitigates of the onset of an EBV-associated disease or disorder.

13. The method of claim 11 or 12, wherein the EBV-associated disease or disorder is selected from the group consisting of a secondary hemophagocytic lymphohistiocytosis (sHLH), cancer, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes (T1D), Macrophage activation syndrome (MAS), chronic NK lymphocytosis, and T cell chronic active EBV (CAEBV).

14. The method of claim 13, wherein the cancer is a heme-based cancer.

15. The method of claim 14, wherein the heme-based cancer is selected from the group consisting of lymphoma, leukemia, and myeloma.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 16. The method of claim 15, wherein the lymphoma is NK cell lymphoma, optionally nasal-type NK cell lymphoma.

17. The method of claim 15, wherein the leukemia is NK cell leukemia.

18. The method of any one of claims 1-17, wherein the subject suffers from one or more additional comorbidities.

19. The method of any one of claims 1-18, wherein the treatment reduces the EBV viral load in the subject.

20. The method of claim 19, wherein the EBV viral load is reduced at least by 10%.

21. The method of claim 20, wherein the EBV viral load is reduced in the blood.

22. The method of claim 20, wherein the EBV viral load is reduced in B cells, T cells, NK cells, or myeloid cells.

23. The method of claim 20, wherein the EBV viral load is reduced in bone marrow.

24. The method of any one of claims 1-23, wherein the treatment results in the depletion of SIRPγ-expressing cells.

25. The method of claim 24, wherein the SIRPγ-expressing cells are B cells, T cells, or NK cells.

26. The method of any one of claims 1-25, wherein the method comprises monitoring EBV viral load, PET-SCANs, C-reactive protein (CRP), sCD25, and / or ferritin peak, minimum, maximum, and reduction prospectively to diagnose and predict prognosis, and / or likelihood of response to therapy for the EBV infection, EBV associated disease or disorder, and / or the one or more additional comorbidities.

27. The method of any one of claims 1-26, wherein the SIRPγ binding antibody is administered to the subject subcutaneously or intravenously.

28. The method of any one of claims 1-27, wherein the administration occurs in a treatment phase.

29. The method of claim 28, wherein the method comprises more than one treatment phase.

30. The method of any one of claims of 1-29, wherein the treatment phase comprises a dose of at least about 0.01 mg / kg to about 5.0 mg / kg of the SIRPγ binding antibody.

31. The method of any claim 30, wherein the treatment phase comprises a dose about 0.1 mg / kg to about 1.0 mg / kg of the SIRPγ binding antibody.

32. The method of any one of claims 1-31, wherein the SIRPγ binding antibody is administered in combination with an additional therapy.Attorney Docket No.: ELTH-011 / 01WO 336159-2069 33. The method of claim 32, wherein the additional therapy is selected from the group consisting of corticosteroids, antiviral agents (e.g., nucleoside analogues), interleukin- 2, interferon alfa, intravenous immunoglobulins, etoposide, and other chemotherapy agents.

34. The method of any one of claims 1-33, wherein the SIRPγ binding antibody is administered in a pharmaceutical composition, wherein the pharmaceutical composition comprises the antibody, and a pharmaceutically acceptable carrier.

35. The method of any one of claims 1-34, wherein the antibody comprises a complementarity determining region (CDR) sequence combination selected from the group consisting of: a. SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220; b. SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226; c. SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232; d. SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238; e. SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244; f. SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250; g. SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256; h. SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262; i. SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268; j. SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 271, SEQ ID NO: 272, SEQ ID NO: 273, SEQ ID NO: 274; k. SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, SEQ ID NO: 278, SEQ ID NO: 279, SEQ ID NO: 280;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 l. SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286; m. SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292; n. SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298; o. SEQ ID NO: 299, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304; p. SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310; q. SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316; r. SEQ ID NO: 317, SEQ ID NO: 318, SEQ ID NO: 319, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322; s. SEQ ID NO: 323, SEQ ID NO: 324, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328; t. SEQ ID NO: 329, SEQ ID NO: 330, SEQ ID NO: 331, SEQ ID NO: 332, SEQ ID NO: 333, SEQ ID NO: 334; u. SEQ ID NO: 335, SEQ ID NO: 336, SEQ ID NO: 337, SEQ ID NO: 338, SEQ ID NO: 339, SEQ ID NO: 340; v. SEQ ID NO: 341, SEQ ID NO: 342, SEQ ID NO: 343, SEQ ID NO: 344, SEQ ID NO: 345, SEQ ID NO: 346; w. SEQ ID NO: 347, SEQ ID NO: 348, SEQ ID NO: 349, SEQ ID NO: 350, SEQ ID NO: 351, SEQ ID NO: 352; x. SEQ ID NO: 353, SEQ ID NO: 354, SEQ ID NO: 355, SEQ ID NO: 356, SEQ ID NO: 357, SEQ ID NO: 358; y. SEQ ID NO: 359, SEQ ID NO: 360, SEQ ID NO: 361, SEQ ID NO: 362, SEQ ID NO: 363, SEQ ID NO: 364; z. SEQ ID NO: 365, SEQ ID NO: 366, SEQ ID NO: 367, SEQ ID NO: 368, SEQ ID NO: 369, SEQ ID NO: 370; aa. SEQ ID NO: 371, SEQ ID NO: 372, SEQ ID NO: 373, SEQ ID NO: 374, SEQ ID NO: 375, SEQ ID NO: 376;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 bb. SEQ ID NO: 377, SEQ ID NO: 378, SEQ ID NO: 379, SEQ ID NO: 380, SEQ ID NO: 381, SEQ ID NO: 382; cc. SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388; dd. SEQ ID NO: 389, SEQ ID NO: 390, SEQ ID NO: 391, SEQ ID NO: 392, SEQ ID NO: 393, SEQ ID NO: 394; ee. SEQ ID NO: 395, SEQ ID NO: 396, SEQ ID NO: 397, SEQ ID NO: 398, SEQ ID NO: 399, SEQ ID NO: 400; ff. SEQ ID NO: 401, SEQ ID NO: 402, SEQ ID NO: 403, SEQ ID NO: 404, SEQ ID NO: 405, SEQ ID NO: 406; gg. SEQ ID NO: 407, SEQ ID NO: 408, SEQ ID NO: 409, SEQ ID NO: 410, SEQ ID NO: 411, SEQ ID NO: 412; hh. SEQ ID NO: 413, SEQ ID NO: 414, SEQ ID NO: 415, SEQ ID NO: 416, SEQ ID NO: 417, SEQ ID NO: 418; ii. SEQ ID NO: 419, SEQ ID NO: 420, SEQ ID NO: 421, SEQ ID NO: 422, SEQ ID NO: 423, SEQ ID NO: 424; jj. SEQ ID NO: 425, SEQ ID NO: 426, SEQ ID NO: 427, SEQ ID NO: 428, SEQ ID NO: 429, SEQ ID NO: 430; kk. SEQ ID NO: 431, SEQ ID NO: 432, SEQ ID NO: 433, SEQ ID NO: 434, SEQ ID NO: 435, SEQ ID NO: 436; ll. SEQ ID NO: 437, SEQ ID NO: 438, SEQ ID NO: 439, SEQ ID NO: 440, SEQ ID NO: 441, SEQ ID NO: 442; mm. SEQ ID NO: 443, SEQ ID NO: 444, SEQ ID NO: 445, SEQ ID NO: 446, SEQ ID NO: 447, SEQ ID NO: 448; nn. SEQ ID NO: 449, SEQ ID NO: 450, SEQ ID NO: 451, SEQ ID NO: 452, SEQ ID NO: 453, SEQ ID NO: 454; oo. SEQ ID NO: 455, SEQ ID NO: 456, SEQ ID NO: 457, SEQ ID NO: 458, SEQ ID NO: 459, SEQ ID NO: 460; pp. SEQ ID NO: 461, SEQ ID NO: 462, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466; qq. SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 470, SEQ ID NO: 471, SEQ ID NO: 472;Attorney Docket No.: ELTH-011 / 01WO 336159-2069 rr. SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478; ss. SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484; tt. SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490; and uu. SEQ ID NO: 491, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, SEQ ID NO: 495, SEQ ID NO:

496.

36. The method of any one of claims 1-35, wherein the SIRPγ binding antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein a. the VH comprises the amino acid sequence of SEQ ID NO: 535, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 536, or an amino acid sequence with at least 80% sequence identity thereto; b. the VH comprises the amino acid sequence of SEQ ID NO: 537, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 538, or an amino acid sequence with at least 80% sequence identity thereto; c. the VH comprises the amino acid sequence of SEQ ID NO: 539, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 540, or an amino acid sequence with at least 80% sequence identity thereto; d. the VH comprises the amino acid sequence of SEQ ID NO: 541, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 542, or an amino acid sequence with at least 80% sequence identity thereto; e. the VH comprises the amino acid sequence of SEQ ID NO: 543, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 544, or an amino acid sequence with at least 80% sequence identity thereto; f. the VH comprises the amino acid sequence of SEQ ID NO: 545, or an amino acid sequence with at least 80% sequence identity thereto, and the VLAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises the amino acid sequence of SEQ ID NO: 546, or an amino acid sequence with at least 80% sequence identity thereto; g. the VH comprises the amino acid sequence of SEQ ID NO: 547, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 548, or an amino acid sequence with at least 80% sequence identity thereto; h. the VH comprises the amino acid sequence of SEQ ID NO: 549, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 550, or an amino acid sequence with at least 80% sequence identity thereto; i. the VH comprises the amino acid sequence of SEQ ID NO: 551, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 552, or an amino acid sequence with at least 80% sequence identity thereto; j. the VH comprises the amino acid sequence of SEQ ID NO: 553, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 554, or an amino acid sequence with at least 80% sequence identity thereto; k. the VH comprises the amino acid sequence of SEQ ID NO: 555, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 556, or an amino acid sequence with at least 80% sequence identity thereto; l. the VH comprises the amino acid sequence of SEQ ID NO: 557, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 558, or an amino acid sequence with at least 80% sequence identity thereto; m. the VH comprises the amino acid sequence of SEQ ID NO: 559, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 560, or an amino acid sequence with at least 80% sequence identity thereto; n. the VH comprises the amino acid sequence of SEQ ID NO: 561, or an amino acid sequence with at least 80% sequence identity thereto, and the VLAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises the amino acid sequence of SEQ ID NO: 562, or an amino acid sequence with at least 80% sequence identity thereto; o. the VH comprises the amino acid sequence of SEQ ID NO: 563, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 564, or an amino acid sequence with at least 80% sequence identity thereto; p. the VH comprises the amino acid sequence of SEQ ID NO: 565, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 566, or an amino acid sequence with at least 80% sequence identity thereto; q. the VH comprises the amino acid sequence of SEQ ID NO: 567, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 568, or an amino acid sequence with at least 80% sequence identity thereto; r. the VH comprises the amino acid sequence of SEQ ID NO: 569, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 570, or an amino acid sequence with at least 80% sequence identity thereto; s. the VH comprises the amino acid sequence of SEQ ID NO: 571, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 572, or an amino acid sequence with at least 80% sequence identity thereto; t. the VH comprises the amino acid sequence of SEQ ID NO: 573, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 574, or an amino acid sequence with at least 80% sequence identity thereto; u. the VH comprises the amino acid sequence of SEQ ID NO: 575, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 576, or an amino acid sequence with at least 80% sequence identity thereto; v. the VH comprises the amino acid sequence of SEQ ID NO: 577, or an amino acid sequence with at least 80% sequence identity thereto, and the VLAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises the amino acid sequence of SEQ ID NO: 578, or an amino acid sequence with at least 80% sequence identity thereto; w. the VH comprises the amino acid sequence of SEQ ID NO: 579, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 580, or an amino acid sequence with at least 80% sequence identity thereto; x. the VH comprises the amino acid sequence of SEQ ID NO: 581, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 582, or an amino acid sequence with at least 80% sequence identity thereto; y. the VH comprises the amino acid sequence of SEQ ID NO: 583, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 584, or an amino acid sequence with at least 80% sequence identity thereto; z. the VH comprises the amino acid sequence of SEQ ID NO: 585, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 586, or an amino acid sequence with at least 80% sequence identity thereto; aa. the VH comprises the amino acid sequence of SEQ ID NO: 587, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 588, or an amino acid sequence with at least 80% sequence identity thereto; bb. the VH comprises the amino acid sequence of SEQ ID NO: 589, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 590, or an amino acid sequence with at least 80% sequence identity thereto; cc. the VH comprises the amino acid sequence of SEQ ID NO: 591, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 592, or an amino acid sequence with at least 80% sequence identity thereto; dd. the VH comprises the amino acid sequence of SEQ ID NO: 593, or an amino acid sequence with at least 80% sequence identity thereto, and the VLAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises the amino acid sequence of SEQ ID NO: 594, or an amino acid sequence with at least 80% sequence identity thereto; ee. the VH comprises the amino acid sequence of SEQ ID NO: 595, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 596, or an amino acid sequence with at least 80% sequence identity thereto; ff. the VH comprises the amino acid sequence of SEQ ID NO: 597, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 598, or an amino acid sequence with at least 80% sequence identity thereto; gg. the VH comprises the amino acid sequence of SEQ ID NO: 599, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 600, or an amino acid sequence with at least 80% sequence identity thereto; hh. the VH comprises the amino acid sequence of SEQ ID NO: 601, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 602, or an amino acid sequence with at least 80% sequence identity thereto; ii. the VH comprises the amino acid sequence of SEQ ID NO: 603, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 604, or an amino acid sequence with at least 80% sequence identity thereto; jj. the VH comprises the amino acid sequence of SEQ ID NO: 605, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 606, or an amino acid sequence with at least 80% sequence identity thereto; kk. the VH comprises the amino acid sequence of SEQ ID NO: 607, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 608, or an amino acid sequence with at least 80% sequence identity thereto; ll. the VH comprises the amino acid sequence of SEQ ID NO: 609, or an amino acid sequence with at least 80% sequence identity thereto, and the VLAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises the amino acid sequence of SEQ ID NO: 610, or an amino acid sequence with at least 80% sequence identity thereto; mm. the VH comprises the amino acid sequence of SEQ ID NO: 611, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 612, or an amino acid sequence with at least 80% sequence identity thereto; nn. the VH comprises the amino acid sequence of SEQ ID NO: 613, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 614, or an amino acid sequence with at least 80% sequence identity thereto; oo. the VH comprises the amino acid sequence of SEQ ID NO: 615, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 616, or an amino acid sequence with at least 80% sequence identity thereto; pp. the VH comprises the amino acid sequence of SEQ ID NO: 617, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 618, or an amino acid sequence with at least 80% sequence identity thereto; qq. the VH comprises the amino acid sequence of SEQ ID NO: 619, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 620, or an amino acid sequence with at least 80% sequence identity thereto; rr. the VH comprises the amino acid sequence of SEQ ID NO: 621, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 622, or an amino acid sequence with at least 80% sequence identity thereto; ss. the VH comprises the amino acid sequence of SEQ ID NO: 623, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 624, or an amino acid sequence with at least 80% sequence identity thereto; tt. the VH comprises the amino acid sequence of SEQ ID NO: 625, or an amino acid sequence with at least 80% sequence identity thereto, and the VLAttorney Docket No.: ELTH-011 / 01WO 336159-2069 comprises the amino acid sequence of SEQ ID NO: 626, or an amino acid sequence with at least 80% sequence identity thereto; and uu. the VH comprises the amino acid sequence of SEQ ID NO: 627, or an amino acid sequence with at least 80% sequence identity thereto, and the VL comprises the amino acid sequence of SEQ ID NO: 628, or an amino acid sequence with at least 80% sequence identity thereto.

37. The method of any one of claims 1-36, wherein the SIRPγ binding antibody comprises an Fc domain.

38. The method of claim 37, wherein the Fc domain is selected from the group consisting of human IgG1, IgG2, IgG3, and IgG4.

39. The method of claim 38, wherein the Fc domain is from the heavy chain IgG amino acid sequences of any one of SEQ ID NOS: 15-46.

40. The method of 39, wherein the heavy chain Fc domain comprises one or more amino acid substitutions relative to SEQ ID NO: 15 or SEQ ID NO: 39 at a position selected from the group consisting of: 215, 221, 222, 228, 234, 235, 236, 239, 240, 241, 243, 244, 245, 247, 250, 252, 254, 256, 262, 263, 264, 265, 266, 267, 268, 269, 270, 292, 296, 297, 298, 299, 300, 305, 313, 324, 325, 326, 327, 328, 329, 330, 332, 333, 334, 345, 396, 428, 430, 433, 434, and 440 wherein the position numbers of the amino acid residues are of the EU numbering scheme.

41. Use of a SIRP^ binding antibody for the treatment of an Epstein-Barr virus (EBV) infection in a subject in need thereof, wherein the SIRP^ binding antibody is specific for SIRP^, and wherein the antibody has low or no affinity for binding SIRPα and SIRPβ.

42. Use of a SIRP^ binding antibody for the manufacture of a medicament for the treatment of an Epstein-Barr virus (EBV) infection in a subject in need thereof, wherein the SIRP^ binding antibody is specific for SIRP^, and wherein the antibody has low or no affinity for binding SIRPα and SIRPβ.

43. A method of treating an Epstein-Barr virus (EBV) infection in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-SIRP^ antibody, wherein the antibody comprises a means for binding human SIRPγ but not SIRPα or SIRPβ.

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