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US 2022/0177593 A1Published application
Anti-axl antibodies and methods of use thereof
AssigneeCelldex Therapeutics, Inc.
InventorsTibor Keler, Diego Alvarado, Richard W. Gedrich, Joel Goldstein, Laura Vitale, Thomas O'Neill, Andrea Crocker, Jenifer Widger, Michael B. Murphy, Shannon Pankratz
Life of this patent
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Abstract
Provided herein are compositions, methods and uses involving antibodies that specifically bind to Axl, a receptor tyrosine kinase. Also provided are uses and methods for managing, treating, or preventing disorders, such as cancer using the anti-Axl antibodies.
Claims161
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising:
- (A) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 20, 21 and 22, respectively, or conservative sequence modifications thereof;
- (B) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 23, 24 and 22, respectively, or conservative sequence modifications thereof;
- (C) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 25, 26 and 22, respectively, or conservative sequence modifications thereof;
- (D) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 33, 34 and 35, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 27, 28 and 29, respectively, or conservative sequence modifications thereof;
- or
- (E) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 123, 124 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 120, 121 and 122, respectively, or conservative sequence modifications thereof.
23 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising:
- (A) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 20, 21 and 22, respectively, or conservative sequence modifications thereof;
- (B) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 23, 24 and 22, respectively, or conservative sequence modifications thereof;
- (C) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 25, 26 and 22, respectively, or conservative sequence modifications thereof;
- (D) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 33, 34 and 35, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 27, 36 and 29, respectively, or conservative sequence modifications thereof;
- or
- (E) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 123, 124 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 120, 121 and 122, respectively, or conservative sequence modifications thereof.
23 more elements
The antibody or antigen-binding fragment of embodiment 9, which specifically binds to human Axl, comprising:
- (A) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 20, 21 and 22, respectively, or conservative sequence modifications thereof;
- (B) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 23, 24 and 22, respectively, or conservative sequence modifications thereof;
- (C) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 25, 26 and 22, respectively, or conservative sequence modifications thereof;
- (D) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 33, 34 and 35, respectively, or conservative sequence modifications thereof;
- and
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 27, 36 and 29, respectively, or conservative sequence modifications thereof;
- or
- (E) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 123, 124 and 32, respectively, or conservative sequence modifications thereof;
- and
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 120, 121 and 122, respectively, or conservative sequence modifications thereof.
23 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising:
- (A) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 20, 21 and 22, respectively, or conservative sequence modifications thereof;
- (B) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 23, 24 and 22, respectively, or conservative sequence modifications thereof;
- (C) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 30, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 25, 26 and 22, respectively, or conservative sequence modifications thereof;
- (D) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 33, 34 and 35, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 27, 37 and 29, respectively, or conservative sequence modifications thereof;
- or
- (E) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 123, 124 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 120, 121 and 122, respectively, or conservative sequence modifications thereof.
23 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising:
- (A) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 38, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 20, 21 and 22, respectively, or conservative sequence modifications thereof;
- (B) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 38, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 23, 24 and 22, respectively, or conservative sequence modifications thereof;
- (C) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 38, 31 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 25, 26 and 22, respectively, or conservative sequence modifications thereof;
- (D) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 39, 34 and 35, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 27, 36 and 29, respectively, or conservative sequence modifications thereof;
- or
- (E) (i) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 130, 124 and 32, respectively, or conservative sequence modifications thereof;
- and/or
- (ii) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprise the amino acid sequences of SEQ ID NOS:
- 120, 121 and 122, respectively, or conservative sequence modifications thereof.
23 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 5.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence of SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence of SEQ ID NO:
- 5.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 7.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence of SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence of SEQ ID NO:
- 7.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 8.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence of SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence of SEQ ID NO:
- 8.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 9.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence of SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence of SEQ ID NO:
- 9.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 10.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence of SEQ ID NO:
- 6;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence of SEQ ID NO:
- 10.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 12;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to SEQ ID NO:
- 11.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to human Axl, comprising a light chain variable region (VL) and a heavy chain variable region (VH), wherein:
- (i) the light chain variable region (VL) comprises an amino acid sequence of SEQ ID NO:
- 12;
- and/or
- (ii) the heavy chain variable region (VH) comprises an amino acid sequence of SEQ ID NO:
- 11.
2 more elements
An isolated antibody, or an antigen-binding fragment thereof, which specifically binds to Ig-like domain 1 in the extracellular domain of human Axl.
An isolated antibody, or an antigen-binding fragment thereof, which binds to Ig-like domain 1 in the extracellular domain of human Axl and inhibits binding of Gas6 to Axl and/or, inhibits Axl phosphorylation.
A human or humanized monoclonal antibody, or an antigen-binding fragment thereof, that preferably binds to Ig-like domain 1 in the extracellular domain of human Axl and which exhibits one or more of the following properties:
- i) binds to human Axl with an affinity constant (equilibrium dissociation constant) KD of 10 nM or less, preferably 5 nM or less or preferably 1 nM or less as determined by bio-layer interferometry;
- ii) binds to human Axl in cells with an EC50 of 1 μg/mL or less, or preferably 0.1 μg/mL or less, as determined by flow cytometry;
- iii) inhibits Gas6 binding to human Axl;
- iv) inhibits Gas6-dependent phosphorylation of Axl, AKT and ERK;
- v) when tested in vitro increases the secretion of Eotaxin-1, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNa2, IFNγ, GRO alpha, IL-10, MCP-3, IL-12P40, MDC, IL-1RA, IL-1B, IL-4, TNFα, RANTES, MIP-1B, IL-6, IL-8, IP-10, VEGF-A, and/or MIP-1a from human monocyte-derived dendritic cells by at least 100% as determined by a Luminex assay when compared to isotype control;
- vi) when tested in vitro increases IL-1RA secretion from human PBMCs by at least 5-fold as determined by ELISA when compared to isotype control;
- vii) when tested in vitro increases IL-1RA secretion from human dendritic cells by at least 2-fold as determined by ELISA when compared to isotype control;
- and
- viii) when tested in vitro increases IL-2 secretion from a co-culture of CD4+ T cells and dendritic cells by at least 40% as determined by ELISA when compared to isotype control.
6 more elements
A method of increasing proinflammatory cytokine production in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that specifically binds to human Axl such that the production of at least one proinflammatory cytokine is increased.
Dependencies are inferred from the claim text.