USRE50631EActiveUtility

ROR1 antibody immunoconjugates

68
Assignee: VELOSBIO INCPriority: Jun 23, 2017Filed: Jul 1, 2021Granted: Oct 14, 2025
Est. expiryJun 23, 2037(~11 yrs left)· nominal 20-yr term from priority
Inventors:Brian LannuttiKatti JessenThanh-Trang VoJeffry D. Watkins
C07K 2317/565A61K 47/6871A61K 45/06A61K 39/3955A61K 2039/572C07K 2317/734A61K 47/6849A61K 47/6811C07K 2317/732C07K 2317/76C07K 2317/24C07K 2317/56A61K 2039/505C07K 2317/92A61K 47/6803A61P 35/00A61K 38/05C07K 16/2803A61K 47/68035A61K 47/68033A61K 47/68031A61P 35/02A61K 47/6817
68
PatentIndex Score
0
Cited by
150
References
99
Claims

Abstract

Provided herein are immunoconjugates comprising an anti-ROR-1 antibody or an antigen-fragment fragment thereof and a drug moiety. These immunoconjugates are useful for treating ROR-1 expressing cancers.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is
 ADC-A, having the structure 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody of the formula:
   Ab-[(L) m -(D)] n    
 
         wherein Ab is an antibody that binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1), and wherein 
         Ab comprises:
 (a) a heavy chain variable region (V H ) comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 8; and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 9, and 
 (b) a light chain variable region (V L ) comprising an LCDRI comprising the amino acid sequence of SEQ ID NO: 10; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 11; and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 12, 
 
         each occurrence of the group -[(L) m -(D)] has the structure: 
       
       
         
           
           
               
               
           
         
         wherein   represents the site of attachment to a sulfur atom on a cysteine residue on [the antibody] Ab; and 
         n is an integer from 1 to 8. 
       
     
     
       2. The immunoconjugate of  claim 1 , wherein the heavy chain and light chain of the antibody Ab  comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       3. The immunoconjugate of  claim 2 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7 n is an integer from 1 to 5. 
     
     
       4. A pharmaceutical composition comprising the immunoconjugate of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
       5. The pharmaceutical composition of  claim 4 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine rapamycin (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       6. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 1 . 
     
     
       7. A method of making the immunoconjugate of  claim 1 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating monomethyl auristatin E (MMAE) to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       8. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-E, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       9. The immunoconjugate of  claim 8 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       10. The immunoconjugate of  claim 8 , wherein the ratio of the cytoxic drug moiety to the antibody is 1 to 7. 
     
     
       11. A pharmaceutical composition comprising the immunoconjugate of  claim 8  and a pharmaceutically acceptable excipient. 
     
     
       12. The pharmaceutical composition of  claim 11 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       13. A method of treating a ROR 1 -expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 8 . 
     
     
       14. A method of making the immunoconjugate of  claim 8 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating monomethyl auristatin E (MMAE) to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:5.   
     
     
       15. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-H, having the structure, 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       16. The immunoconjugate of  claim 15 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       17. The immunoconjugate of  claim 16 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       18. A pharmaceutical composition comprising the immunoconjugate of  claim 15  and a pharmaceutically acceptable excipient. 
     
     
       19. The pharmaceutical composition of  claim 18 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton'tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2(Bcl-2) inhibitor, mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       20. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 15 . 
     
     
       21. A method of making the immunoconjugate of  claim 15 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating azonafide to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO: 6.   
     
     
       22. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-J, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       23. The immunoconjugate of  claim 22 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       24. The immunoconjugate of  claim 23 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       25. A pharmaceutical composition comprising the immunoconjugate of  claim 22  and a pharmaceutically acceptable excipient. 
     
     
       26. The pharmaceutical composition of  claim 25 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (MTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       27. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 22 . 
     
     
       28. A method of making the immunoconjugate of  claim 22 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating Duocarmycin TM to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       29. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-K, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       30. The immunoconjugate of  claim 29 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       31. The immunoconjugate of  claim 30 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       32. A pharmaceutical composition comprising the immunoconjugate of  claim 29  and a pharmaceutically acceptable excipient. 
     
     
       33. The pharmaceutical composition of  claim 32 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       34. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 29 . 
     
     
       35. A method of making the immunoconjugate of  claim 29 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating pyrrolobenzodiazepine (PBD) to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       36. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-L, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       37. The immunoconjugate of  claim 36 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       38. The immunoconjugate of  claim 37 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       39. A pharmaceutical composition comprising the immunoconjugate of  claim 36  and a pharmaceutically acceptable excipient. 
     
     
       40. The pharmaceutical composition of  claim 39 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       41. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 36 . 
     
     
       42. A method of making the immunoconjugate of  claim 36 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating monomethyl auristatin E (MMAE) to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       43. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-M, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       44. The immunoconjugate of  claim 43 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       45. The immunoconjugate of  claim 44 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       46. A pharmaceutical composition comprising the immunoconjugate of  claim 43  and a pharmaceutically acceptable excipient. 
     
     
       47. The pharmaceutical composition of  claim 46 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       48. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 43 . 
     
     
       49. A method of making the immunoconjugate of  claim 43 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating monomethyl auristatin E (MMAE) to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       50. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-N, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       51. The immunoconjugate of  claim 50 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       52. The immunoconjugate of  claim 51 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       53. A pharmaceutical composition comprising the immunoconjugate of  claim 50  and a pharmaceutically acceptable excipient. 
     
     
       54. The pharmaceutical composition of  claim 53 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       55. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 50 . 
     
     
       56. A method of making the immunoconjugate of  claim 50 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating PNU-159682 to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       57. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-O, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       58. The immunoconjugate of  claim 57 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       59. The immunoconjugate of  claim 58 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       60. A pharmaceutical composition comprising the immunoconjugate of  claim 57  and a pharmaceutically acceptable excipient. 
     
     
       61. The pharmaceutical composition of  claim 60 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       62. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 57 . 
     
     
       63. A method of making the immunoconjugate of  claim 57 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating PNU-159682 to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       64. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-P, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       65. The immunoconjugate of  claim 64 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       66. The immunoconjugate of  claim 65 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       67. A pharmaceutical composition comprising the immunoconjugate of  claim 64  and a pharmaceutically acceptable excipient. 
     
     
       68. The pharmaceutical composition of  claim 67 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       69. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 64 . 
     
     
       70. A method of making the immunoconjugate of  claim 64 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating PNU-159682 to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       71. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-Q, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       72. The immunoconjugate of  claim 71 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       73. The immunoconjugate of  claim 72 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       74. A pharmaceutical composition comprising the immunoconjugate of  claim 71  and a pharmaceutically acceptable excipient. 
     
     
       75. The pharmaceutical composition of  claim 74 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       76. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 71 . 
     
     
       77. A method of making the immunoconjugate of  claim 71 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating monomethyl auristatin E (MMAE) to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       78. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H  and V L  of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-R, having the structure 
       
         
           
           
               
               
           
         
         wherein Ab in the structure is the antibody. 
       
     
     
       79. The immunoconjugate of  claim 78 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively. 
     
     
       80. The immunoconjugate of  claim 79 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7. 
     
     
       81. A pharmaceutical composition comprising the immunoconjugate of  claim 78  and a pharmaceutically acceptable excipient. 
     
     
       82. The pharmaceutical composition of  claim 81 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor. 
     
     
       83. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of  claim 78 . 
     
     
       84. A method of making the immunoconjugate of  claim 78 , comprising:
 providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and   conjugating PNU-159682 to the antibody;   wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.   
     
     
       85. The immunoconjugate of  claim 3 , wherein n is 4.  
     
     
       86. The immunoconjugate of  claim 1 , wherein Ab comprises: a heavy chain comprising an amino acid sequence at least 95% identical to that of SEQ ID NO: 3, and a light chain comprising an amino acid sequence at least 95% identical to that of SEQ ID NO: 4. 
     
     
       87. A method of treating a human receptor tyrosine kinase like orphan receptor 1 (ROR1) expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 1. 
     
     
       88. A method of making the immunoconjugate of  claim 1 , comprising the steps:
 (i) reducing the cysteine residues of Ab of claim 1 by contacting Ab with a reducing agent; and   (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).   
     
     
       89. The method of  claim 87 , wherein the human receptor tyrosine kinase like orphan receptor 1 (ROR1) expressing cancer is a lymphoma. 
     
     
       90. The method of  claim 89 , wherein the lymphoma is selected from diffuse large β-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). 
     
     
       91. The method of  claim 87 , further comprising administering to the patient one or more additional therapeutic agents, wherein the one or more additional therapeutic agents are selected from rituximab, cyclophosphamide, vincristine, prednisone, gemcitabine, daunorubicin hydrochloride, and a Bruton's tyrosine kinase (BTK) inhibitor. 
     
     
       92. The immunoconjugate of  claim 86 , wherein Ab comprises: a V H  comprising the amino acid sequence of SEQ ID NO: 5, and a V L  comprising the amino acid sequence of SEQ ID NO: 6. 
     
     
       93. A method of making the immunoconjugate of  claim 3 , comprising the steps:
 (i) reducing the cysteine residues of Ab of claim 3 by contacting Ab with a reducing agent; and   (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).   
     
     
       94. A method of making the immunoconjugate of  claim 86 , comprising the steps:
 (i) reducing the cysteine residues of Ab of claim 86 by contacting Ab with a reducing agent; and   (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).   
     
     
       95. A method of making the immunoconjugate of  claim 92 , comprising the steps:
 (i) reducing the cysteine residues of Ab of claim 92 by contacting Ab with a reducing agent; and   (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).   
     
     
       96. The immunoconjugate of  claim 86 , wherein n is 4. 
     
     
       97. The immunoconjugate of  claim 92 , wherein n is 4. 
     
     
       98. The method of  claim 90 , wherein the lymphoma is diffuse large β-cell lymphoma (DLBCL). 
     
     
       99. The method of  claim 98 , further comprising administering to the patient one or more additional therapeutic agents, wherein the one or more additional therapeutic agents are selected from rituximab, cyclophosphamide, vincristine, prednisone, daunorubicin hydrochloride, and gemcitabine.

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