# US 2014/0193385 A1 · Method for stimulating a host immune system

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- Number: US 2014/0193385 A1
- Document ID: US20140193385A1
- Status: Published application
- Kind: A1
- Application number: 14/206,785
- Filed: 2014-03-12
- Published: 2014-07-10
- Earliest claimed: 2003-05-13
- Assignees: Immunovative Therapies Ltd.
- Applicants: Immunovative Therapies, Ltd.
- Inventors: Michael Har-Noy
- Web page: https://patentgrep.com/patent/US20140193385A1

## 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 protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “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 effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, 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 in methods to stimulate host immunity. The method includes a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and/or radiation conditioning regimens.

## Claims

### Claim 1

A method of treating a diseased host comprising:
stimulating the host's Type I adaptive immunity and generating de novo tumor associated antigen (TAA) shedding in the host wherein the stimulating is performed by the administration of activated allogeneic CD4+ cells.

### Claim 2 (depends on 1)

The method of claim 1 wherein the CD4+ cells comprise cross-linked CD3 and CD28 surface molecules.

### Claim 3 (depends on 1)

The method of claim 1 wherein the method further comprises activation and upregulation of cytotoxic activity of the host's NK cells.

### Claim 4 (depends on 1)

The method of claim 1 wherein the TAA shedding is by apoptosis of the tumors.

### Claim 5 (depends on 4)

The method of claim 4 wherein apoptosis is induced by binding of Fas with FasL.

### Claim 6 (depends on 4)

The method of claim 4 wherein apoptosis is induced by TRAIL ligand and TRAIL-R.