# US 12,213,962 B2 · Drug resistant immunotherapy for treatment of a cancer

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- Number: US 12,213,962 B2
- Document ID: US12213962B2
- Status: Granted
- Kind: B2
- Application number: 16/708,180
- Filed: 2019-12-09
- Published: 2020-10-15
- Granted: 2025-02-04
- Earliest claimed: 2009-11-02
- Assignees: Emory University; The UAB Research Foundation; Children's Healthcare of Atlanta, Inc.
- Applicants: Emory University; The UAB Research Foundation; Children's Healthcare of Atlanta, Inc.
- Inventors: Harold Trent Spencer; Anindya Dasgupta; Lawrence S. Lamb
- Web page: https://patentgrep.com/patent/US12213962B2

## CPC

- A61K 31/4188: condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells
- A61K 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- C12N 5/0636: {T lymphocytes}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C12N 2510/00: Genetically modified cells
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure is generally related to methods for combining chemotherapy and immunotherapy for the treatment of a cancer. The methods also relate to generating a drug-resistant cytotoxic immune cell line and uses thereof in conjunction with cytotoxic drugs

## Claims

### Claim 1

A composition comprising a carrier and isolated natural killer (NK) cells, wherein greater than about 50% of the NK cells express a heterologous polypeptide that confers resistance to a chemotherapy agent, and wherein the NK cells that express the heterologous polypeptide are present in a therapeutically effective amount.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the heterologous polypeptide that confers resistance to a chemotherapy agent is O6-methylguanine DNA methyltransferase (MGMT), a drug resistant variant of dihydrofolate reductase (L22Y-DHFR), thymidylate synthase, or multiple drug resistance-1 protein (MDRI).

### Claim 3 (depends on 1)

The composition of claim 1, wherein the heterologous polypeptide that confers resistance to the chemotherapy agent is O6-methylguanine DNA methyltransferase (MGMT).

### Claim 4 (depends on 1)

The composition of claim 1, wherein the chemotherapy agent induces production of a stress protein in a cancer cell of a patient, and wherein the stress protein is recognized by the NK cells.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the composition is formulated for injection into a patient.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the chemotherapy agent is temozolomide and the heterologous polypeptide conferring resistance to the chemotherapy agent is O6-methylguanine DNA methyltransferase (MGMT).

### Claim 7 (depends on 1)

The composition of claim 1, wherein the heterologous polypeptide that confers resistance to a chemotherapy agent is thymidylate synthase or multiple drug resistance-I protein (MDRI).

### Claim 8

A composition comprising a carrier and isolated NK cells wherein greater than about 50% of the NK cells comprise a nucleic acid that encodes a heterologous polypeptide, wherein upon expression of the heterologous polypeptide by the NK cell, the heterologous polypeptide confers resistance to a chemotherapy agent, and wherein the NK cells that comprise the nucleic acid that encodes the heterologous polypeptide are present in a therapeutically effective amount.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the heterologous polypeptide that confers resistance to a chemotherapy agent is O6-methylguanine DNA methyltransferase (MGMT), a drug resistant variant of dihydrofolate reductase (L22Y-DHFR), thymidylate synthase, or multiple drug resistance-1 protein (MDRI).

### Claim 10 (depends on 9)

The composition of claim 9, wherein the heterologous polypeptide that confers resistance to a chemotherapy the chemotherapy agent is O6-methylguanine DNA methyltransferase (MGMT).

### Claim 11 (depends on 8)

The composition of claim 8, wherein the chemotherapy agent induces production of a stress protein in a cancer cell of a patient, and wherein the stress protein is recognized by the NK cells.

### Claim 12 (depends on 8)

The composition of claim 8, wherein the composition is formulated for injection into a patient.

### Claim 13 (depends on 9)

The composition of claim 9, wherein the chemotherapy agent is temozolomide and the heterologous polypeptide conferring resistance to the chemotherapy agent is O6-methylguanine DNA methyltransferase (MGMT).

### Claim 14 (depends on 9)

The composition of claim 9, wherein the heterologous polypeptide that confers resistance to a chemotherapy agent is thymidylate synthase or multiple drug resistance-I protein (MDRI).