US 12,378,530 B2
Methods to preserve tumor-stromal interactions in culture and therapeutic predictive applications thereof
James Neal, San Mateo, CA (US); and Calvin Jay Kuo, Palo Alto, CA (US)
Assigned to The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Filed by The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Filed on Oct. 22, 2021, as Appl. No. 17/508,474.
Application 17/508,474 is a continuation of application No. 15/793,249, filed on Oct. 25, 2017, granted, now 11,180,735.
Claims priority of provisional application 62/414,549, filed on Oct. 28, 2016.
Prior Publication US 2022/0041994 A1, Feb. 10, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/09 (2010.01); A61K 39/395 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); G01N 33/50 (2006.01); G01N 33/574 (2006.01); A61K 39/00 (2006.01)
CPC C12N 5/0693 (2013.01) [A61K 39/39558 (2013.01); C07K 16/2818 (2013.01); C12N 5/0636 (2013.01); G01N 33/5011 (2013.01); G01N 33/5047 (2013.01); G01N 33/57484 (2013.01); A61K 2039/505 (2013.01); G01N 2800/50 (2013.01)] 17 Claims
 
1. A method for identifying a candidate agent as an immunotherapeutic effective to activate tumor-infiltrating immune cells in a patient's tumor, the method comprising:
obtaining or providing a tumor tissue sample comprising stromal and immune cells obtained from the patient's tumor;
culturing the tumor tissue sample in a gel with an air-liquid interface such that a patient specific organoid (PDO) with stromal and immune cell elements is formed;
contacting the PDO with the candidate agent for a period of time sufficient to modulate tumor-infiltrating immune cell activity;
determining an effect of the candidate agent on tumor-infiltrating immune cell activity; and
identifying the candidate agent as an immunotherapeutic effective to activate tumor-infiltrating immune cells in the patient's tumor when the tumor-infiltrating immune cell activity is increased relative to a control PDO that is not contacted with the candidate agent.