Methods and compositions for treating breast cancer using antisense

Patent metadata

Field	Value
Publication number	US-2022000916-A1
Application number	US-201917290799-A
Country	US
Kind code	A1
Filing date	Oct 31, 2019
Priority date	Nov 2, 2018
Publication date	Jan 6, 2022
Grant date	—

Abstract

The present disclosure relates to compositions and methods for treating breast cancer using antisense (AS) nucleic acids directed against Insulin-like Growth Factor 1 Receptor (IGF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. In embodiments, the AS are provided in an implantable irradiated biodiffusion chamber comprising tumor cells and an effective amount of the AS. The chambers are irradiated and implanted in the abdomen of subjects and stimulate an immune response that attacks tumors distally. The compositions and methods disclosed herein may be used to treat many different kinds of breast cancer, including metastatic breast cancer.

First claim

1 . A method for preparing a biodiffusion chamber for implantation into a subject having breast cancer, the method comprising:
(a) encapsulating tumor cells obtained from the subject into the biodiffusion chamber in the presence of an IGF-1R AS ODN;
wherein the tumor cells are obtained from the subject using a tissue morselator, and
(b) irradiating the biodiffusion chamber.

2 . The method of claim 1 , wherein the breast cancer is at least one selected from the group consisting of hormone receptor negative, triple-negative breast cancer, and metastatic breast cancer.

3 .- 4 . (canceled)

5 . The method of claim 1 , wherein the subject has a genetic mutation in one or more of the following genes: BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, TP53 (p53).

6 . The method of claim 1 , wherein the tumor cells are dispersed before adding to the chamber.

7 . The method of claim 1 , wherein the cells are not exposed to temperatures above body temperature during removal from the subject.

8 . (canceled)

9 . The method of claim 1 , wherein the tissue morselator comprises at least one selected from the group consisting of a sterile trap and a high-speed reciprocating inner cannula within a stationary outer cannula.

10 . (canceled)

11 . The method of claim 1 , wherein the outer cannula comprises a side aperture, and further wherein the tumor cells are drawn into the side aperture by electronically controlled variable suction.

12 . The method of claim 1 , wherein the tumor cells are enriched for nestin expression before they are placed into the biodiffusion chamber.

13 . The method of claim 1 , wherein the tumor cells in the chamber are enriched for adherent cells compared to the tumor cells obtained from the subject.

14 . (canceled)

15 . The method of claim 1 , wherein the cells are treated with IGF-1R AS ODN before encapsulation into the chamber.

16 .- 19 . (canceled)

20 . The method of claim 1 , wherein the IGF-1R AS ODN has the sequence of SEQ ID NO:1.

21 . A method of treating a subject having breast cancer, comprising implanting two or more biodiffusion chambers according to claim 1 into the subject.

22 . The method of claim 21 , wherein about 10 to about 30 biodiffusion chambers are implanted into the subject.

23 . (canceled)

24 . The method of claim 21 , wherein the diffusion chambers are implanted into the subject for 48 hours.

25 . The method of claim 21 , wherein the breast cancer is at least one selected from hormone receptor negative, triple-negative breast cancer, and metastatic breast cancer.

26 .- 27 . (canceled)

28 . The method of claim 21 , wherein the subject has a genetic mutation in one or more of the following genes: BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, TP53 (p53).

29 . The method of claim 21 , wherein the method is performed without chemotherapy, without radiation therapy, or without both.

30 . The method of claim 21 , comprising a second implantation of chambers subsequent to the first implantation.

31 . The method of claim 30 , wherein the second implantation comprises at least one selected from the group consisting of:
a) a second implantation that uses tumor cells obtained from the subject at the same time as those cells obtained from the first administration, and b) a second implantation that uses tumor cells obtained from the subject after the first treatment is complete and the tumor has recurred or not responded to the first treatment.

32 . (canceled)

33 . A method of vaccinating a subject having a breast cancer comprising:
(i) obtaining morselized tumor tissue from the subject; (ii) collecting the morselized tissue in a sterile trap; (iii) harvesting adherent cells from the morselized tissue; (iv) encapsulating the harvested cells in a biodiffusion chamber along with insulin-like growth factor receptor-1 antisense oligodeoxynucleotide (IGF-1R AS ODN) having the sequence of SEQ ID NO:1; (v) irradiating the chamber, and (vi) implanting the chamber in the subject, wherein an immune response against the breast cancer is obtained.

34 . The method of claim 33 , wherein the breast cancer is at least one selected from the group consisting of hormone receptor-negative, triple-negative breast cancer, and metastatic breast cancer.

35 .- 36 . (canceled)

37 . The method of claim 33 , wherein the subject has a genetic mutation in one or more of the following genes: BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, TP53 (p53).

38 . The method of claim 33 , comprising the step of treating the adherent cells with IGF-1R AS ODN for up to 18 hours prior to encapsulation.

39 . The method of claim 33 , wherein the subject is vaccinated with 20 chambers for about 48 hours.

40 . The method of claim 33 , wherein the tumor cells are not exposed to temperatures above body temperature.

41 . A biodiffusion chamber for implantation into a subject having breast cancer, the biodiffusion chamber comprising:
(a) irradiated tumor cells,
wherein the tumor cells comprise adherent cells obtained from the subject's tumor tissue;
wherein the tumor cells are pre-incubated with insulin-like growth factor receptor-1 antisense oligodeoxynucleotide (IGF-1R AS ODN) prior to encapsulation within the chamber; and
(b) irradiated IGF-1R AS ODN wherein the IGF-1R AS ODN has the sequence of SEQ ID NO:1.

42 . The biodiffusion chamber of claim 41 , wherein the breast cancer is at least one selected from the group consisting of hormone receptor-negative breast cancer, triple-negative breast cancer, and metastatic breast cancer.

43 .- 44 . (canceled)

45 . The biodiffusion chamber of claim 41 , wherein the subject has a genetic mutation in one or more of the following genes: BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, TP53 (p53).

46 . The biodiffusion chamber of claim 41 , wherein the tumor cells in the chamber are enriched for Nestin-positive cells compared to the tumor tissue obtained from the subject.

47 . The biodiffusion chamber of claim 41 , wherein about 10 6 tumor cells are present in the chamber.

48 . The biodiffusion chamber of claim 41 , wherein the tumor cells are obtained from the subject using a tissue morselator.

49 .- 50 . (canceled)

Assignees

• Univ Jefferson

Inventors

• Hooper Douglas Craig
• Andrews David
• Lebrun Aurore

Classifications

• C12N5/0012 Primary

  Cell encapsulation · CPC title

• A61K35/13 Primary

  Tumour cells, irrespective of tissue of origin (tumour vaccines A61K39/00) · CPC title

• C12N5/0693

  Tumour cells; Cancer cells · CPC title

• C12N2510/00

  Genetically modified cells · CPC title

• C12N2501/105

  Insulin-like growth factors [IGF] · CPC title