# US 11,077,141 B2 · Anti-tumor T cell immunity induced by high dose radiation

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- Number: US 11,077,141 B2
- Document ID: US11077141B2
- Status: Granted
- Kind: B2
- Application number: 16/202,769
- Filed: 2018-11-28
- Published: 2019-03-21
- Granted: 2021-08-03
- Earliest claimed: 2012-08-30
- Assignees: The Board of Trustees of the Leland Stanford Junior University
- Applicants: The Board of Trustees of the Leland Stanford Junior University
- Inventors: Samuel Strober; Alexander Filatenkov
- Web page: https://patentgrep.com/patent/US11077141B2

## CPC

- A61K 41/00: Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations}
- 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 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/42: Cancer antigens
- A61K 41/0023: {Aggression treatment or altering}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- A61P 35/00: Antineoplastic agents
- C12N 5/0636: {T lymphocytes}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/49: Breast
- A61K 2239/50: Colon
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- 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

Cancer treatment is provided, by irradiating an individual with a localized, high single dose or short course of doses at a primary tumor site; collecting T cells from the individual after a period of time sufficient activation of an anti-tumor response; treating the individual with an effective dose of dose of chemotherapy; and reintroducing the T cell population back to the individual.

## Claims

### Claim 1

A method for treating a cancer in a subject, the method comprising:
a. activating T cells with a high dose of localized radiation at a tumor site;
b. collecting a population of cells comprising the activated T cells and hematopoietic stem cells; and
c. administering the collected population of cells to the subject, thereby treating the cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the high dose of localized radiation comprises a total dose of 20 to 40 Gy.

### Claim 3 (depends on 2)

The method of claim 2, wherein the high dose of localized radiation is delivered in a single dose.

### Claim 4 (depends on 2)

The method of claim 2, wherein the high dose of localized radiation is delivered in fractionated doses over a period of time of not more than one week.

### Claim 5 (depends on 1)

The method of claim 1, wherein (a) is performed over a time period from 2 to 6 weeks.

### Claim 6 (depends on 1)

The method of claim 1, further comprising purifying the activated T cells from regulatory T cells and purge tumor cells in the collected population of cells.

### Claim 7 (depends on 1)

The method of claim 1, wherein the collected population of cells comprises allogeneic cells.

### Claim 8 (depends on 1)

The method of claim 1, wherein the collected population of cells comprises autologous cells.

### Claim 9 (depends on 1)

The method of claim 1, wherein the collected population of cells comprises CD34+ cells.

### Claim 10 (depends on 1)

The method of claim 1, wherein activated T cells comprises CD8+ T cells, wherein the CD8+ T cells are activated by the high dose of localized radiation at the tumor site to recognize the cancer.

### Claim 11 (depends on 1)

The method of claim 1, wherein the collected population of cells comprises at least 1×106 CD8+ T cells.

### Claim 12 (depends on 11)

The method of claim 11, further comprising enriching the CD8+ T cells from the collected population of cells.

### Claim 13 (depends on 11)

The method of claim 11, further comprising purifying the CD8+ T cells from the collected population of cells.

### Claim 14 (depends on 1)

The method of claim 1, wherein administering the collected population of cells provides for durable remission of the cancer.

### Claim 15 (depends on 1)

The method of claim 1, wherein administering the collected population of cells prevents growth of metastases at a site other than the tumor.

### Claim 16 (depends on 1)

The method of claim 1, wherein administering the collected population of cells stimulates an immune system of the subject to target cancer cells.

### Claim 17 (depends on 1)

The method of claim 1, wherein the cancer is in an advanced state.

### Claim 18 (depends on 1)

The method of claim 1, wherein the cancer is metastatic.

### Claim 19 (depends on 1)

The method of claim 1, wherein the subject has been treated with an effective dose of chemotherapy prior to administering the collected population of cells.

### Claim 20 (depends on 19)

The method of claim 19 wherein the effective dose of chemotherapy is a non-myeloablative dose.

### Claim 21 (depends on 19)

The method of claim 19, wherein the effective dose of chemotherapy is a myeloablative dose.

### Claim 22 (depends on 1)

The method of claim 1, wherein the cancer is a liver cancer, a lung cancer, a brain cancer, a pancreas cancer, a melanoma cancer, or a breast cancer.

### Claim 23 (depends on 1)

The method of claim 1, wherein the subject is a mammal.
