Methods for determining efficacy of chemotherapeutic agents

Abstract

An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined.

1 . A method for assessing chemosensitivity of patient cells comprising the steps of:
 a) harvesting a specimen of a patient's tissue, cells ascites, or effusion fluid;   b) separating said specimen into multicellular particulates;   c) growing a tissue culture monolayer from said cohesive multicellular particulates;   d) inoculating cells from said monolayer into a plurality of segregated sites; and   e) treating said plurality of sites with at least one active agent, followed by assessment of chemosensitivity of the cells in said site to at least one active agent.   
     
     
         2 . The method according to  claim 1  wherein step a) further comprises the step of
 a) preparing a specimen which was harvested from a sample of patient tumor tissue. 
 
     
     
         3 . The method according to  claim 1  wherein said plurality of segregated sites further comprises a plate containing a plurality of wells therein. 
     
     
         4 . The method according to  claim 1  wherein step e) further comprises the step of:
 e) treating said plurality of sites with a plurality of active agents at varied concentrations, followed by assessment of optimal chemosensitivity with respect to a single active agent at a single concentration. 
 
     
     
         5 . The method according to  claim 1  wherein step e) further comprises the step of:
 e) treating said plurality of sites with a plurality of active agents over a length of time adequate to permit assessment of both initial cytotoxic effect and longer-term inhibitory effect of at least one of said plurality of active agents. 
 
     
     
         6 . The method according to  claim 1  wherein the chemosensitivity assayed according to step e) is anti-cancer sensitivity. 
     
     
         7 . The method according to  claim 1  wherein step d) is accomplished using a Terasaki dispenser. 
     
     
         8 . The method according to  claim 1  wherein the cells in step d) are prepared in suspension prior to inoculation into a plurality of wells in a culture plate. 
     
     
         9 . The method according to  claim 1 , wherein said active agent is a chemotherapeutic agent. 
     
     
         10 . The method according to  claim 1 , wherein said active agent is a wound healing agent. 
     
     
         11 . The method according to  claim 1 , wherein said active agent is a radiation therapy and/or a radiation therapy sensitizing or ameliorating agent. 
     
     
         12 . The method according to  claim 1 , where said active agent is an immunotherapeutic agent.