Immunotherapy with combination therapy comprising an immunotoxin

Patent metadata

Field	Value
Publication number	US-12514927-B2
Application number	US-202017773494-A
Country	US
Kind code	B2
Filing date	Oct 29, 2020
Priority date	Oct 30, 2019
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

Provided is a combination and a method of using combination therapy to treat tumor in an individual. An immunotoxin and an immunostimulator are administered to the individual, wherein the immunotoxin comprises a single chain variable region antibody fused to a PE38 truncated Pseudomonas exotoxin, and the immunostimulator comprises an anti-CD40 agonist antibody. The combination may further comprise a checkpoint inhibitor comprising one or more of an anti-PD-1 antibody and an anti-PD-L1 antibody.

First claim

We claim:

1 . A method of treating a solid tumor expressing one or more of EGFRwt and EGFRvIII in an individual, comprising:
administering to the individual a therapeutically effective amount of an immunotoxin comprising a single chain variable region antibody fused to a truncated Pseudomonas exotoxin comprising PE38, wherein the single chain variable region antibody comprises a variable heavy chain comprising CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3 and a variable light chain comprising CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5 and CDR3 of SEQ ID NO: 6; and concurrently administering a therapeutically effective amount of an anti-CD40 agonist antibody to the individual, wherein the immunotoxin and anti-CD40 agonist antibody are administered intratumorally.

2 . The method of claim 1 , further comprising administering to the individual a therapeutically effective amount of a checkpoint inhibitor comprising one or more of an anti-PD1 antibody or anti-PD-L1 antibody.

3 . The method of claim 2 , wherein the checkpoint inhibitor is administered within 30 days of administering the immunotoxin.

4 . The method of claim 2 , wherein the checkpoint inhibitor is administered within between 7 and 14 days of administering the immunotoxin.

5 . The method of claim 1 , wherein the tumor is a malignant glioma.

6 . The method of claim 1 , wherein the tumor is breast cancer.

7 . The method of claim 1 , wherein the tumor is head and neck squamous cell carcinoma.

8 . The method of claim 1 , wherein the tumor is lung cancer.

9 . The method of claim 1 , wherein the truncated Pseudomonas exotoxin is fused to a KDEL (SEQ ID NO:14) peptide.

10 . The method of claim 1 , further comprising repeated administration of a therapeutically effective amount of an anti-CD40 agonist antibody to the individual.

11 . The method of claim 10 , wherein the repeated administration of the anti-CD40 agonist antibody is administered subcutaneously.

12 . A kit for treating a tumor, comprising:
an immunotoxin comprising a single chain variable region antibody fused to a truncated Pseudomonas exotoxin comprising PE38, wherein the single chain variable region antibody has a variable heavy chain comprising CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3 and a variable light chain comprising CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6; and an anti-CD40 agonist antibody, wherein the immunotoxin and anti-CD40 agonist antibody are formulated for intratumoral delivery.

13 . The kit of claim 12 , wherein the truncated Pseudomonas exotoxin is fused to a KDEL (SEQ ID NO: 14) peptide.

14 . The kit of claim 12 , further comprising a checkpoint inhibitor comprising one or more of an anti-PD-1 antibody and an anti-PD-L1 antibody.

15 . A composition formulated for intratumoral delivery comprising an immunotoxin comprising a single chain variable region antibody fused to a truncated Pseudomonas exotoxin comprising PE38, wherein the single chain variable region antibody has a variable heavy chain comprising CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3 and a variable light chain comprising CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6; and an anti-CD40 agonist antibody.

16 . The composition of claim 15 , further comprising a checkpoint inhibitor comprising one or more of an anti-PD-1 antibody and an anti-PD-L1 antibody.

Assignees

• Univ Duke
• Us Secretary Department Of Health And Human Services

Inventors

• Bigner Darell
• Chandramohan Vidyalakshmi
• Pastan Ira H

Classifications

• C07K2317/75

  Agonist effect on antigen · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title