US 12,276,664 B2
Method for classifying cancer patients into appropriate hepatocellular carcinoma treatment groups and compounds for treating the patient
Suk Peng Chew, Singapore (SG); Salvatore Albani, Singapore (SG); Kah-Hoe Pierce Chow, Singapore (SG); and Lu Pan, Singapore (SG)
Assigned to SINGAPORE HEALTH SERVICES PTE. LTD., Singapore (SG)
Appl. No. 16/768,001
Filed by SINGAPORE HEALTH SERVICES PTE. LTD., Singapore (SG)
PCT Filed Nov. 29, 2018, PCT No. PCT/SG2018/050585
§ 371(c)(1), (2) Date May 28, 2020,
PCT Pub. No. WO2019/108135, PCT Pub. Date Jun. 6, 2019.
Claims priority of application No. 10201709924T (SG), filed on Nov. 30, 2017.
Prior Publication US 2021/0341483 A1, Nov. 4, 2021
Int. Cl. G01N 33/574 (2006.01); A61K 51/12 (2006.01)
CPC G01N 33/57438 (2013.01) [A61K 51/1251 (2013.01); G01N 33/57492 (2013.01)] 8 Claims
 
1. An ex vivo method for the prognosis of response to treatment for a patient suffering from hepatocellular carcinoma, the method comprising:
creating a prediction model comprising;
Measuring expression of a plurality of immune markers on each cell in samples taken from a plurality of patients with hepatocellular carcinoma;
Evaluating a clinical response of the patients with hepatocellular carcinoma to treatment with radioembolization (RE) at 3 and/or 6 months after treatment wherein the clinical response is selected from sustained responder (SR) to RE, and transient/non-responder (TR/NR) to RE;
Determining if there is a correlation between each immune marker and either the clinical response SR, or the clinical response TR/NR;
Determining the probability of each immune marker one by one to positively affect the accuracy of the clinical response;
allocating a probability score using a weighted neighbourhood scheme, to each sample based on the number of immune markers that positively affects the accuracy of the clinical response;
measuring expression of at least one immune marker in a leukocyte sample taken from the patient with hepatocellular carcinoma;
allocating the same probability score obtained using the weighted neighbourhood scheme for each immune marker in the leukocyte sample taken from the patient suffering from hepatocellular carcinoma to classify the patient suffering from cancer as a predicted SR or predicted TR/NR,
further classifying the patient leukocyte sample into (i) SR to RE or (ii) TR/NR to RE based on evaluating the expression of the at least one immune marker on each cell in the leukocyte sample; wherein a sample is classified as SR, when equal to or greater than 50% of the cells in the sample express the at least one marker, and a sample is classified as TR/NR when less than 50% of the cells express the at least one marker;
wherein the at least one immune marker comprises co-expression of CD8 and PD-1, or co-expression of CD8 and CCR5; or co-expression of CD8 and Tim-3, or co-expression of CD8 and CXCR6, or co-expression of CD8 and Tim-3 with CCR5, or expression of CD8 and Tim-3, with CXCR6
whereby patient predicted to be a SR is administered treatment with selective internal radiation therapy (SIRT) alone or SIRT in combination with immunotherapy and patient predicted to be TR/NR is administered treatment with trans-arterial chemoembolization (TACE), Sorafenib or immunotherapy alone.