GRP78-binding antibodies and use thereof in detecting or neutralizing GRP78
AssigneeRutgers, The State University of New Jersey
InventorsRenata Pasqualini, Wadih Arap, Fernanda I. Staquicini, Fortunato Ferrara, Sara D'Angelo, Andrew R.M. Bradbury
Life of this patent
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Abstract
Isolated or recombinant EphA5 or GRP78 targeting antibodies are provided. In some cases, antibodies of the embodiments can be used for the detection, diagnosis and/or therapeutic treatment of human diseases, such as cancer. A method of rapidly identifying antibodies or antibody fragments for the treatment of cancer using a combination of in vitro and in vivo methodologies is also provided.
Claims31
An isolated monoclonal antibody, wherein the antibody specifically binds to glucose regulated protein 78 (GRP78) and comprises:
- (a) a first VH CDR at least 80% identical to VH CDR1 of B4 (SEQ ID NO. 39);
- (b) a second VH CDR at least 80% identical to VH CDR2 of B4 (SEQ ID NO. 40);
- (c) a third VH CDR at least 80% identical to VH CDR3 of B4 (SEQ ID NO. 41);
- (d) a first VL CDR at least 80% identical to VL CDR1 of B4 (SEQ ID NO. 42);
- (e) a second VL CDR at least 80% identical to VL CDR2 of B4 (SEQ ID NO. 43);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of B4 (SEQ ID NO. 44).
An isolated monoclonal antibody, wherein the antibody specifically binds to glucose regulated protein 78 (GRP78) and comprises:
- (a) a first VH CDR at least 80% identical to VH CDR1 of F6 (SEQ ID NO. 55);
- (b) a second VH CDR at least 80% identical to VH CDR2 of F6 (SEQ ID NO. 56);
- (c) a third VH CDR at least 80% identical to VH CDR3 of F6 (SEQ ID NO. 57);
- (d) a first VL CDR at least 80% identical to VL CDR1 of F6 (SEQ ID NO. 58);
- (e) a second VL CDR at least 80% identical to VL CDR2 of F6 (SEQ ID NO. 59);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of F6 (SEQ ID NO. 60).
A composition comprising a recombinant antibody, and at least one pharmaceutically acceptable carrier, wherein the antibody specifically binds to glucose regulated protein 78 (GRP78) and comprises:
- (a) a first variable heavy (VH) complementary determining region (CDR) at least 80% identical to VH CDR1 of B4 (SEQ ID NO. 39);
- (b) a second VH CDR at least 80% identical to VH CDR2 of B4 (SEQ ID NO. 40);
- (c) a third VH CDR at least 80% identical to VH CDR3 of B4 (SEQ ID NO. 41);
- (d) a first variable light (VL) CDR at least 80% identical to VL CDR1 of B4 (SEQ ID NO. 42);
- (e) a second VL CDR at least 80% identical to VL CDR2 of B4 (SEQ ID NO. 43);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of B4 (SEQ ID NO. 44).
A composition comprising a recombinant antibody and at least one pharmaceutically acceptable carrier, wherein the antibody specifically binds to glucose regulated protein 78 (GRP78) and comprises:
- (a) a first variable heavy (VH) complementary determining region (CDR) at least 80% identical to VH CDR1 of F6 (SEQ ID NO. 55);
- (b) a second VH CDR at least 80% identical to VH CDR2 of F6 (SEQ ID NO. 56);
- (c) a third VH CDR at least 80% identical to VH CDR3 of F6 (SEQ ID NO. 57);
- (d) a first variable light (VL) CDR at least 80% identical to VL CDR1 of F6 (SEQ ID NO. 58);
- (e) a second VL CDR at least 80% identical to VL CDR2 of F6 (SEQ ID NO. 59);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of F6 (SEQ ID NO. 60).
A method for treating or ameliorating cancer in a subject, the method comprising administering to the subject an effective amount of an isolated monoclonal antibody, wherein the isolated monoclonal antibody specifically binds to glucose regulated protein 78 (GRP78) and comprises:
- (a) a first VH CDR at least 80% identical to VH CDR1 of B4 (SEQ ID NO. 39);
- (b) a second VH CDR at least 80% identical to VH CDR2 of B4 (SEQ ID NO. 40);
- (c) a third VH CDR at least 80% identical to VH CDR3 of B4 (SEQ ID NO. 41);
- (d) a first VL CDR at least 80% identical to VL CDR1 of B4 (SEQ ID NO. 42);
- (e) a second VL CDR at least 80% identical to VL CDR2 of B4 (SEQ ID NO. 43);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of B4 (SEQ ID NO. 44).
A method for treating or ameliorating cancer in a subject, the method comprising administering to the subject an effective amount of an isolated monoclonal antibody, wherein the isolated monoclonal antibody specifically binds to glucose regulated protein 78 (GRP78) and comprises:
- (a) a first VH CDR at least 80% identical to VH CDR1 of F6 (SEQ ID NO. 55);
- (b) a second VH CDR at least 80% identical to VH CDR2 of F6 (SEQ ID NO. 56);
- (c) a third VH CDR at least 80% identical to VH CDR3 of F6 (SEQ ID NO. 57);
- (d) a first VL CDR at least 80% identical to VL CDR1 of F6 (SEQ ID NO. 58);
- (e) a second VL CDR at least 80% identical to VL CDR2 of F6 (SEQ ID NO. 59);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of F6 (SEQ ID NO. 60).
A method for detecting cancer in a subject, the method comprising testing for the presence of elevated GRP78 levels in a sample from the subject relative to a control, wherein the testing comprises contacting the sample from the subject with an isolated monoclonal antibody, wherein the isolated monoclonal antibody specifically binds to GRP78 and comprises:
- (a) a first VH CDR at least 80% identical to VH CDR1 of B4 (SEQ ID NO. 39);
- (b) a second VH CDR at least 80% identical to VH CDR2 of B4 (SEQ ID NO. 40);
- (c) a third VH CDR at least 80% identical to VH CDR3 of B4 (SEQ ID NO. 41);
- (d) a first VL CDR at least 80% identical to VL CDR1 of B4 (SEQ ID NO. 42);
- (e) a second VL CDR at least 80% identical to VL CDR2 of B4 (SEQ ID NO. 43);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of B4 (SEQ ID NO. 44).
A method for detecting cancer in a subject, the method comprising testing for the presence of elevated GRP78 levels in a sample from the subject relative to a control, wherein the testing comprises contacting the sample from the subject with an isolated monoclonal antibody, wherein the isolated monoclonal antibody specifically binds to GRP78 and comprises:
- (a) a first VH CDR at least 80% identical to VH CDR1 of F6 (SEQ ID NO. 55);
- (b) a second VH CDR at least 80% identical to VH CDR2 of F6 (SEQ ID NO. 56);
- (c) a third VH CDR at least 80% identical to VH CDR3 of F6 (SEQ ID NO. 57);
- (d) a first VL CDR at least 80% identical to VL CDR1 of F6 (SEQ ID NO. 58);
- (e) a second VL CDR at least 80% identical to VL CDR2 of F6 (SEQ ID NO. 59);
- and
- (f) a third VL CDR at least 80% identical to VL CDR3 of F6 (SEQ ID NO. 60).
Dependencies are inferred from the claim text.