Human immune therapies using a cd27 agonist in combination with another immune agonist to treat cancer

Patent metadata

Field	Value
Publication number	US-2018273631-A1
Application number	US-201815934334-A
Country	US
Kind code	A1
Filing date	Mar 23, 2018
Priority date	Oct 20, 2006
Publication date	Sep 27, 2018
Grant date	—

Abstract

Methods of inducing T cell proliferation and expansion in vivo for treating conditions wherein antigen-specific T cell immune response are therapeutically desirable such as cancer, infection, inflammation, allergy and autoimmunity and for enhancing the efficacy of vaccines are provided. These methods comprise the administration of at least one CD27 agonist, preferably an agonistic CD27 antibody, alone or in association with another moiety such as immune stimulant or immune modulator such as an anti-CD40, OX-40, 4-1BB, or CTLA-4 antibody or an agent that depletes regulatory cells, or a cytokine. These mono and combination therapies may also optionally include the administration of a desired antigen such as a tumor antigen, an allergen, an autoantigen, or an antigen specific to an infectious agent or pathogen against which a T cell response (often CD8+) is desirably elicited.

First claim

1 . An agonistic anti-human CD27 antibody or an antigen binding fragment thereof.

2 . The agonistic antibody of claim 1 which comprises one of more of the following:
(i) it recognizes an extracellular portion of human CD70;
(ii) the binding of said antibody is not appreciably affected by human CD70 or CD70-related ligands;
(iii) it is selected from a human antibody, a chimeric antibody, a humanized antibody, bispecific antibody, primatized antibody and a single chain antibody;
(iv) it is attached to an effector moiety;
(v) it contains at least one human constant domain selected from IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD, and IgE constant domains;
(vi) is engineered to modify (enhance or diminish) at least one antibody effector function;
(vii) it is engineered to modify at least one of Fc glycosylation, binding to FcR, binding to FeRn, or complement binding;
(viii) it promotes T cell immune responses; or (ix) it promotes Th1 immune responses.

3 - 10 . (canceled)

11 . A method of promoting immunity in a subject in need thereof comprising administering at least one CD27 agonistic antibody according to claim 1 to a subject with a condition or treatment wherein enhanced immunity is therapeutically desirable in an amount effective to promote immunity.

12 . The method of claim 11 which comprises one or more of the following:
(i) it enhances Th1 immunity;
(ii) it promotes the proliferation or survival of antigen-specific T cells;
(iii) it promotes the proliferation or survival of antigen-specific CD8 + T cells;
(iv) it promotes the proliferation or survival of antigen-specific CD8 + effector cells, or memory cells;
(v) it results in the generation of antigen-specific memory T cells;
(vi) it includes the administration of antigen;
(vii) the administered anti-CD27 antibody or antigen binding fragment promotes the expansion of T cells in an antigen-dependent manner;
(viii) the administered anti-CD27 antibody or antigen binding fragment is selected from a human antibody, primate antibody, chimeric antibody, humanized antibody, primatized antibody and single chain antibody;
(ix) the administered anti-CD27 antibody or antigen binding fragment is engineered to modify (enhance or diminish) at least one antibody effector function;
(x) the administered anti-CD27 antibody or antigen binding fragment (1) lacks glycosylation,
(xi) the administered anti-CD27 antibody or antigen binding fragment is modified to alter Fc glycosylation, (3) it comprises one or more Fc residue modifications, (4) it is modified to enhance or diminish binding to a specific FcR or (5) it comprises a combination of the foregoing modifications;
(xii) the administered anti-CD27 antibody or antigen binding fragment is modified to enhance or inhibit FcRn binding;
(xiii) the administered anti-CD27 antibody or antigen binding fragment comprises modifications that are selected from (1) modifications that reduce or enhance interaction with proteins of the complement system, or (2) modifications which reduce undesirable toxicity;
(xiv) the administered anti-CD27 antibody or antigen binding fragment is modified to inhibit toxicity elicited by release of cytokines;
(xv) the administered anti-CD27 antibody or antigen binding fragment contains at least one of human IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD and IgE constant domains;
(xvi) the administered anti-CD27 antibody or antigen binding fragment is an intact antibody selected from a group consisting of an intact IgG1 antibody, an intact IgG2 antibody, an intact IgG3 antibody, an intact IgG4 antibody, and intact IgM antibody, an intact IgA1 antibody, an intact IgA2 antibody, an intact secretory IgA antibody, an intact IgD antibody, or an intact IgE antibody;
(xvii) the administered anti-CD27 antibody or antigen binding fragment is used to treat a condition selected from cancer, infectious disease, inflammatory condition, autoimmune disease, and allergic condition;
(xviii) the administered anti-CD27 antibody or antigen binding fragment is used to treat an infectious disease caused by a bacterium, virus, mycobacterium, fungus, yeast or a parasite.
(xix) the administered anti-CD27 antibody or antigen binding fragment is used to treat an infectious disease caused by a parasite selected from Babesia sp., Entomoeba sp, Giarda sp, Plasmodium sp, Leishmania sp, Trypanosome sp, Toxoplasma sp, flatworm and round worm parasites; or a bacterium is selected from Escherichia, Staphylococcus, Pseudomonas, Streptococcus, Campylobacter, Listeria, Clostridium, Pasteurella, Pseudomonas, Neisseria, Enterococcus, Klebsiella, Heliobacter, Listeria, Salmonella, Corynebacterium, Haemophilus, Pasteurella, Bacteroides, Fusobacterium, Streptobacillus, Treponema, Leptospira, Rickettsia , and Actinomyces or a virus is selected from a retrovirus, picornavirus, enterovirus, hepatitis, poliovirus, Coxsackie's virus, rhinovirus, echovirus, Calciviridae, Togaviridae, Flaviviridae, Rhabdoviridae, Coronaviridae, Paramyxoviridae, Orthomyxoviridae, Filoviridae, Bungaviridae, Reoviridae, Adenoviridae, Bimaviridae, Papovaviridae, Herpeviridae, Iridoviridae, and unclassified viruses; or a fungus selected from Aspergillus, Coccidoides, Blastomyces, Histoplasma, Chlamydia, Nocardia , and Pneumocytis;
(xx) the administered anti-CD27 antibody or antigen binding fragment is used to treat a cancer selected from lymphoma, leukemia, chronic lymphocytic leukemia, breast cancer, prostate cancer, colon cancer, bone cancer, pancreatic cancer, stomach cancer, liver cancer, cervical cancer, bladder cancer, testicular cancer, kidney cancer, lung cancer (small and large cell), brain cancer, retinoblastoma, esophageal cancer, eye cancer, head and neck cancer, endometrial cancer, larynx cancer, melanoma, neuroblastoma, neuroblastoma, thyroid cancer, rhabdosarcoma, oral cavity cancer, uterine cancer, ovarian cancer, sarcoma, connective tissue cancer and skin cancer;
(xxi) the administered anti-CD27 antibody or antigen binding fragment is used to treat an autoimmune disease selected from multiple sclerosis, diabetes, psoriasis, Crohn's disease, inflammatory bowel disease, SLE, myasthenia gravis, Goodpasture's syndrome, ITP, Graves disease, hemolytic anemia, rheumatoid arthritis, Hashimoto's thyroiditis, scleroderma, and Addison's disease;
(xxii) the administered anti-CD27 antibody or antigen binding fragment is administered in a subject that is further administered a vaccine and the anti-CD27 antibody or antigen binding fragment enhances the immune response elicited by said vaccine;
(xxiii) the administered anti-CD27 antibody or antigen binding fragment is administered in a subject that is further administered an antitumor vaccine and the anti-CD27 antibody or antigen binding fragment enhances the antitumor immune response elicited by said vaccine;
(xxiv) the administered anti-CD27 antibody or antigen binding fragment is administered to a subject that is further administered a vaccine for affording immunity against an infectious agent and the anti-CD27 antibody or antigen binding fragment enhances the immune response elicited by said vaccine against the infectious agent optionally selected from a bacterium, a virus, a yeast, a fungus, a mycobacteria, or a parasite;
(xxv) the administered anti-CD27 antibody or antigen binding fragment is administered in conjunction with at least one antigen or allergen;
(xxvi) the administered anti-CD27 antibody or antigen binding fragment is administered before, after or in conjunction with a vaccine composition or is combined with the vaccine as a combined composition, optionally wherein the vaccine is a viral vaccine that confers immunity to a virus selected from a hepatitis, HIV, picornavirus, poliovirus, enterovirus, human Coxsackie virus, influenza virus, rhinovirus, echovirus, rubel

Assignees

• Univ Southampton

Inventors

• Glennie Martin John
• Tutt Alison Louise
• Al-Shamkhani Aymen

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/04

  Immunostimulants · CPC title