# US 8,541,185 B2 · Method of predicting responsiveness to autologous adoptive cell transfer therapy

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- Number: US 8,541,185 B2
- Document ID: US8541185B2
- Status: Granted
- Kind: B2
- Application number: 12/679,696
- Filed: 2008-09-15
- Published: 2010-12-09
- Granted: 2013-09-24
- Earliest claimed: 2007-09-24
- Assignees: Technion Research & Development Foundation Limited; Tel HaShomer Medical Research Infrastructure and Services Ltd.
- Applicants: Kfir Oved; Eran Eden; Martin Akerman; Roy Noy; Michal Besser; Yoram Reiter
- Inventors: Kfir Oved; Eran Eden; Martin Akerman; Roy Noy; Michal Besser; Yoram Reiter
- Web page: https://patentgrep.com/patent/US8541185B2

## CPC

- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- A61P 35/00: Antineoplastic agents
- G01N 33/505: {involving T-cells}
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A method of determining responsiveness to cancer treatment is disclosed. The method comprises analyzing a frequency of tumor infiltrating lymphocytes (TILs) having a CD8+CD28−CD152− signature in a sample of the subject, wherein a frequency of TILs having the CD8+CD28−CD152− signature above a predetermined level is indicative of a positive responsiveness to cancer treatment. Other signatures reflecting responsiveness to cancer treatment are also disclosed. In addition, methods of treating cancer based on these signatures are also disclosed.

## Claims

### Claim 1

A method of predicting responsiveness to autologous adoptive cell transfer therapy in a subject having metastatic melanoma, the method comprising contacting tumor infiltrating lymphocytes (TILs) of a tumor sample isolated from the subject with an antibody which recognizes CD8, an antibody which recognizes CD28 and an antibody which recognizes CD152 so as to determine a frequency of TILs having a CD8+CD28−CD152− signature, wherein a frequency of TILs having said CD8+CD28-CD152− signature below 25% is predicative of a negative responsiveness to autologous adoptive cell transfer therapy.

### Claim 2 (depends on 1)

The method of claim 1, further comprising analyzing a frequency of TILs having a CD8+CD69+CD33− signature in the tumor sample of the subject, wherein a frequency of TILs having said CD8+CD69+CD33− signature above 60% and a CD8+CD28−CD152− signature above 45% is predicative of a negative responsiveness to autologous adoptive cell transfer therapy.

### Claim 3 (depends on 1)

The method of claim 1, further comprising analyzing a frequency of TILs having a CD94+ signature in the sample, wherein a frequency of TILs having said CD8+CD28−CD152− signature below 25%, whilst having a CD94+ signature above 0.7% is further indicative of a negative responsiveness to adoptive cell transfer therapy.