# US 2014/0154278 A1 · Method for allogeneic cell therapy

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- Number: US 2014/0154278 A1
- Document ID: US20140154278A1
- Status: Published application
- Kind: A1
- Application number: 14/173,494
- Filed: 2014-02-05
- Published: 2014-06-05
- Earliest claimed: 2004-05-04
- Assignees: Immunovative Therapies Ltd.
- Applicants: Immunovative Therapies, Ltd.
- Inventors: Michael Har-Noy
- Web page: https://patentgrep.com/patent/US20140154278A1

## CPC

- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- 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 40/30: characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K 40/42: Cancer antigens
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/12: Antivirals
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C12N 5/0636: {T lymphocytes}
- A61K 40/50: characterised by the use of allogeneic cells
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- C12N 2501/51: B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
- C12N 2501/515: CD3, T-cell receptor complex
- C12N 2531/00: Microcarriers
- C12N 2533/40: Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
- 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

A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.

## Claims

### Claim 1

A method of allogeneic transplant into a host that provides an anti-tumor effect without GVHD toxicity to the host, the method comprising:
infusing into the host allogeneic cells of which at least a portion are activated T-cells derived from a tissue mis-matched normal donor and wherein said allogeneic cells are rejected by the host.

### Claim 2 (depends on 1)

The method of claim 1 wherein at least a portion of the allogeneic T-cells are Th1 cells.

### Claim 3 (depends on 1)

The method of claim 1 wherein the allogeneic T-cells are activated by cross-linking CD3 and CD28 surface antigens.

### Claim 4

A method for stimulating a host immune response against a tumor comprising:
selecting cells from a normal donor of which at least a portion are T-cells;
activating and formulating said donor cells ex vivo in media suitable for infusion into a host cancer patient; and
administering said activated donor cells to the host who has a 50% or less tissue match to said normal donor.

### Claim 5 (depends on 4)

The method of claim 4 wherein the host immune response against the tumor includes the production of a “cytokine storm” including at least one of the following cytokines: IL-2, IL-15, TNF-alpha, TNF-beta, IL-12 and IFN-gamma.

### Claim 6 (depends on 5)

The method of claim 5 wherein the selected normal donor cells are frozen prior to activation.

### Claim 7 (depends on 4)

The method of claim 4 wherein said cells are activated by CD3 and CD28 surface antigen cross-linking.

### Claim 8 (depends on 4)

The method of claim 4 wherein the host immune response against the tumor includes activating innate cells including NK cells or macrophages.

### Claim 9

A method for stimulating a coupled host vs. tumor and host vs. graft effect in a host which mirrors the coupled graft vs. tumor and graft vs. host effects of allogeneic transplant procedures comprising:
selecting a composition of donor allogeneic cells; and
administering said allogeneic cells to the host who has not been pre-conditioned with immunosuppressive treatment.

### Claim 10 (depends on 9)

The method of claim 9 wherein the composition of allogeneic cells include T-cells.

### Claim 11 (depends on 10)

The method of claim 10 wherein the T-cells are predominately CD4+ T-cells.

### Claim 12 (depends on 11)

The method of claim 11 wherein the CD4+ T-cells are predominantly Th1 cells.

### Claim 13 (depends on 9)

The method of claim 9 wherein the T-cells are activated at the time of infusion.

### Claim 14 (depends on 20)

The method of claim 20 wherein the T-cells are activated by cross-linking of CD3 and CD28 surface antigens.