Vaccines against an oncogenic isoform of HER2 (ErbB2) and methods of using the same

Patent metadata

Field	Value
Publication number	US-12083172-B2
Application number	US-202016953221-A
Country	US
Kind code	B2
Filing date	Nov 19, 2020
Priority date	Jul 7, 2014
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

Methods of reducing the likelihood of a cancer or precancer developing resistance to a cancer therapeutic or prevention agent are provided herein. The methods include administering a vaccine comprising a polynucleotide encoding a polypeptide whose expression or activation is correlated with development of resistance of the cancer or precancer to the cancer therapeutic or prevention agent to a subject. The vaccine may include a polynucleotide encoding a HER2 polypeptide or a truncation, deletion or substitution mutant thereof. Methods of using the vaccine including the polynucleotide encoding the HER2 polypeptide to treat a cancer or precancer are also provided. The vaccines may be administered with a cancer therapeutic or prevention agent or a checkpoint inhibitor immunomodulatory agent.

First claim

We claim:

1. A method of treating a HER2d16 containing cancer or precancer or of reducing the likelihood of the HER2d16 containing cancer developing resistance to a cancer therapeutic or prevention agent comprising administering a vaccine to a subject having the HER2d16 containing cancer or precancer, wherein the vaccine comprises a polynucleotide encoding a mutant HER2 polypeptide, wherein the HER2 polypeptide consists of SEQ ID NO: 4 or SEQ ID NO: 6, wherein administration of the vaccine to the subject treats the cancer or precancer, reduces the likelihood of the HER2d16 containing cancer or precancer developing resistance to the cancer therapeutic or prevention agent or reverses resistance of the cancer or precancer to the cancer therapeutic or prevention agent.

2. The method of claim 1 , wherein the vaccine is administered concurrently with, before or after administration of the cancer therapeutic or prevention agent.

3. The method of claim 2 , wherein the cancer therapeutic or prevention agent is an agent targeting HER2, HER1, estrogen receptor, or IGF1R.

4. The method of claim 1 , wherein the vaccine is administered concurrently with, before or after administration of a checkpoint inhibitor immunomodulatory agent.

5. The method of claim 4 , wherein the checkpoint inhibitor immunomodulatory agent is a CTLA-4 or PD1 antagonistic antibody.

6. The method of claim 1 , wherein the cancer or precancer is selected from a breast, prostate, lung, ovarian, colon, rectal, pancreas, bladder, head and neck or liver cancer or precancer.

7. The method of claim 1 , wherein the subject develops an immune response to HER2 after administration of the vaccine.

8. The method of claim 7 , wherein the immune response comprises an antibody response or a T cell mediated response.

9. The method of claim 7 , wherein the immune response includes at least one of antibody-dependent cellular cytotoxicity, polyclonal antibody response, complement dependent cellular cytotoxicity, cellular cytotoxicity, disruption of ligand binding, disruption of dimerization, mimicking ligand binding causing internalization of HER2, or degradation of HER2.

10. The method of claim 1 , wherein administration of the vaccine results in a reduction of HER2 expression on cancer or precancer cells after administration of the vaccine as compared to a level of HER2 on the cells prior to vaccination.

11. The method of claim 1 , wherein administration results in decreased tumor growth rate or decreased tumor size after administration as compared to prior to administration.

12. The method of claim 1 , wherein the cancer therapeutic or prevention agent is selected from trastuzumab, lapatinib, cetuximab, pertuzumab and erlotinib.

Assignees

• Univ Duke

Inventors

• Lyerly Herbert K
• Osada Takuya
• Hartman Zachary C

Classifications

• C12Y207/10001

  Receptor protein-tyrosine kinase (2.7.10.1) · CPC title

• C12N2740/15043

  viral genome or elements thereof as genetic vector · CPC title

• C12N2740/15034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title