Compositions, methods, and computer systems related to making and administering modified t cells

Abstract

Embodiments described herein relate to methods, devices, and computer systems thereof for the derivation of T CAR libraries (Universal Subject or Individual Subject) for personalized treatment of disease in a subject. In certain embodiments, differential screening of normal and diseased tissue expression data is utilized to determine disease-specific antigens and thereby generate T CAR cells reactive to such antigens to form a disease-specific library. In certain embodiments, determination of the most effective T CAR clones from the disease-specific library is based on the subject's own disease-specific antigens. In certain embodiments, a subject is treated with a therapeutically effective amount of T CAR clones.

What is claimed is: 
     
         1 .- 49 . (canceled) 
     
     
         50 . A system, comprising:
 one or more input/output devices having a non-transitory signal bearing medium operable to   accept at least one input related to gene expression information from one or more non-diseased tissue antigens from two or more subjects;   accept at least one input related to gene expression information from one or more diseased tissue antigens from two or more subjects;   compare the input related to gene expression information from one or more non-diseased tissue antigens from two or more subjects with the input related to gene expression information from the corresponding one or more diseased tissue antigens, from two or more subjects;   generate a differential antigen value based on the comparison;   reinitiate accepting at least one input related to gene expression information from one or more non-diseased tissue antigens from two or more subjects, and comparing with the input related to gene expression information from the corresponding gene of the one or more diseased tissue antigens until a differential threshold is satisfied based on a predetermined functional avidity; and   generate a Universal Subject Disease-Specific Antigen dataset for the differential antigen values.   
     
     
         51 . The system of  claim 50 , further comprising: communicate to a user an output including a Universal Subject Disease-Specific Antigen dataset representative of a differential antigenic profile based on the comparison. 
     
     
         52 . The system of  claim 50 , wherein the differential threshold includes one or more of: differential temporal or spatial expression of the one or more antigens in the diseased tissue, absence of expression of the one or more antigens in the diseased tissue, differential quantity of expression of the one or more antigens in the diseased tissue, or differential quality of expression of the one or more antigens in the diseased tissue. 
     
     
         53 . The system of  claim 50 , wherein the comparing the input, related to gene expression information from one or more non-diseased tissue antigens from two or more subjects with the input related to gene expression information of the corresponding one or more diseased tissue antigens from two or more subjects comprises: at least one of coupling, versioning, or clustering in determining the differential antigen value. 
     
     
         54 . The system of  claim 50 , wherein the input/output device is operable to convert light emissions into electronic signals that include one or more digitized or weighted images, datasets, or protocols. 
     
     
         55 .- 56 . (canceled) 
     
     
         57 . The system of  claim 50 , wherein the gene expression information comprises: information related to primary, secondary, or tertiary characteristics of two or more epitopes of the one or more non-diseased tissue antigens or the one or more diseased tissue antigens, or degree of affinity to which a particular scFv matches the level of expression of a particular antigen on a cell. 
     
     
         58 . The system of  claim 50 , further comprising: determine at least one recognition domain for at least two epitopes of the one or more diseased tissue antigens. 
     
     
         59 . The system of  claim 50 , further comprising: generate an output to a user including the at least one recognition domain for the at least two epitopes of the one or more diseased tissue antigens indicative of a multi-specific T cell Chimeric Antigen Receptor. 
     
     
         60 . (canceled) 
     
     
         61 . The system of  claim 50 , further comprising transmitting at least some information related to the gene expression information of one or more non-diseased tissue antigens or diseased tissue antigens to one or more databases. 
     
     
         62 . (canceled) 
     
     
         63 . The system of  claim 50 , further comprising: generate a selection of one or more diseased tissue antigens from the Universal Subject Disease-Specific Antigen dataset based on the comparison. 
     
     
         64 . A system, comprising:
 one or more input/output devices having a non-transitory signal bearing medium operable to   accept at least one input related to gene expression information from one or more non-diseased tissue antigens from a diseased subject to, be treated;   accept at least one input related to gene expression information from one or more diseased tissue antigens from the diseased subject to be treated;   compare the input related to gene expression information from the one or more non-diseased tissue antigens from the diseased subject with the input related to gene expression information from the corresponding one or more diseased tissue antigens from the diseased subject;   generate a differential antigen value based on the comparison;   reinitiate accepting at least one input related to gene expression information from one or more non-diseased tissue antigens from the diseased subject, and compare with the input related to gene expression information of the corresponding gene of the one or more diseased tissue antigens until a differential threshold is satisfied based on a predetermined functional avidity; and   generate an Individual Subject Disease-Specific Antigen dataset for the differential antigen values.   
     
     
         65 . The system of  claim 64 , further comprising: communicate to a user an output including the Individual Subject Disease-Specific Antigen dataset representative of a differential antigenic profile based on the comparison. 
     
     
         66 . The system of  claim 64 , wherein the Individual Subject Disease-Specific Antigen dataset comprises: one or more genetic or mRNA sequences that, correlate to the one or more diseased tissue antigens. 
     
     
         67 . The system of  claim 64 , further including comprising: identify one or more recognition domains of two or more epitopes of the one or more diseased tissue antigens based on the genetic or mRNA sequences. 
     
     
         68 . The system of  claim 64 , further comprising: select two or more recognition domains of two or more epitopes of the one or more diseased tissue antigens as representative of a multi-specific T cell Chimeric Antigen Receptor specifically reactive to the one or more diseased tissue antigens. 
     
     
         69 . The system of  claim 64 , further comprising: determine one or more parameters for making or administering one or more T cells bearing the multi-specific Chimeric Antigen Receptor. 
     
     
         70 . The system of  claim 69 , further comprising: determine one or more parameters for dosing or administration schedule for administering the one or more T cells to the diseased subject. 
     
     
         71 .- 72 . (canceled) 
     
     
         73 . A method executed on a computing device, comprising:
 accepting data related to a subject;   receiving at least one input related to gene expression information from one or more non-diseased tissue antigens from two or more subjects;   receiving at least one input related to gene expression information from one or more diseased tissue antigens from two or more subjects;   comparing the input related to gene expression information from one or more non-diseased tissue antigens from two or more subjects with the input related to gene expression information from the corresponding one or more diseased, tissue antigens from two or more subjects;   generating a differential antigen value based on the comparison;
 reinitiating accepting at least one input related to, gene expression information from one or more non-diseased tissue antigens from two or more subjects, and comparing with the input related to gene expression information from the corresponding gene of the one or more diseased tissue antigens until a differential threshold is satisfied based on a predetermined functional avidity; and 
 generating a Universal Subject Disease-Specific Antigen dataset for the differential antigen values. 
   
     
     
         74 . The method of  claim 73 , wherein the one or more characteristics of the subject include one or more of genetic or mRNA sequence of one or more antigens, or post-translational modification of one or more antigens. 
     
     
         75 . The method of  claim 73 , further comprising: storing the Universal Subject Disease-Specific Antigen Value(s). 
     
     
         76 . (canceled) 
     
     
         77 . The method of  claim 73 , further comprising: transmitting one or more signals in response to generating a Universal Subject Disease-Specific Antigen dataset. 
     
     
         78 .- 79 . (canceled) 
     
     
         80 . A method, executed on a computing device, comprising:
 accepting data related to a subject;   receiving at least one input related to gene expression information from one or more non-diseased tissue antigens from a diseased subject to be treated;   receiving at least one input related to gene expression information from one or more diseased tissue antigens from the diseased subject to be treated;   comparing the input related to gene expression information from the one or more non-diseased tissue antigens from the diseased subject with the input related to gene expression information from the corresponding one or more diseased tissue antigens from the diseased subject;   generating a differential antigen value based on the comparison;
 reinitiating accepting at least one input related to gene expression information from one or more non-diseased tissue antigens from the diseased subject, and comparing with the input related to gene expression information of the corresponding gene of the one or more diseased tissue antigens until a differential threshold is satisfied based on a predetermined functional avidity; and 
   generating an Individual Subject Disease-Specific Antigen dataset for the differential antigen values.   
     
     
         81 . The method of  claim 80 , further comprising: transmitting one or more signals in response to generating an Individual Subject Disease-Specific Antigen dataset. 
     
     
         82 .- 85 . (canceled)