Methods for selecting therapy for a cancer patient

A method of selecting a therapy for a cancer patient, the method comprising:

• detecting a mutation in one or more polypeptides in a cancer cell from the patient which is not present in a noncancerous cell,
• wherein the mutation decreases activity of the polypeptide;
• and
• wherein the one or more polypeptides is encoded by a gene selected from the group consisting of PTCD2, TWF1, DEFB134, BBS1, SOX10, APLNR, CD58, COL17A1, CRKL, hsa-mir-101-2, hsa-mir-548s, MAD2L1, MLANA, PSMB5, RNPS1, RPL10A, RPL23, SRP54, TAF3, TAP1, TAP2, TAPBP, TBXAS1, GMIP, OTOA, LAIR1, CLEC1, GPSM3, TRAF1, JAK2, TAPBPL, ICAM1, LILRA1, LILRA3, STAT1, and HLA-F;
• selecting the patient for a therapy which is not a T cell therapy when the mutation is present in the cancer cell;
• and
• selecting the patient for a T cell therapy when the mutation is not present in the cancer cell.

A method of selecting a therapy for a cancer patient, the method comprising:

• measuring a level of one or both of (i) mRNA and (ii) polypeptide expressed from one or more genes in a cancer cell from the patient, wherein the one or more genes is selected from the group consisting of PTCD2, TWF1, DEFB134, BBS1, SOX10, APLNR, CD58, COL17A1, CRKL, hsa-mir-101-2, hsa-mir-548s, MAD2L1, MLANA, PSMB5, RNPS1, RPL10A, RPL23, SRP54, TAF3, TAP1, TAP2, TAPBP, TBXAS1, GMIP, OTOA, LAIR1, CLEC1, GPSM3, TRAF1, JAK2, TAPBPL, ICAM1, LILRA1, LILRA3, STAT1, and HLA-F;
• measuring the level of one or both of (i) mRNA and (ii) polypeptide expressed from the same one or more genes in a noncancerous cell;
• comparing the level of one or both of (i) mRNA and (ii) polypeptide measured in the cancer cell with the level of one or both of (i) mRNA and (ii) polypeptide, respectively, measured in the noncancerous cell;
• selecting the patient for a therapy which is not a T cell therapy when the level of one or both of (i) mRNA and (ii) polypeptide measured in the cancer cell is decreased as compared to the level of one or both of (i) mRNA and (ii) polypeptide, respectively, measured in the noncancerous cell;
• and
• selecting the patient for a T cell therapy when the level of one or both of (i) mRNA and (ii) polypeptide measured in the cancer cell is not decreased as compared to the level of one or both of (i) mRNA and (ii) polypeptide, respectively, measured in the noncancerous cell.

A method of screening for one or more genes, the mutation of which confers resistance to T cell-mediated cytolytic activity, the method comprising:

• introducing a nucleic acid encoding a Cas endonuclease and a nucleic acid encoding a single guide RNA (sgRNA) molecule into a target cell, wherein the sgRNA hybridizes to a test gene in the target cell,
• forming a complex between the sgRNA and Cas endonuclease so that the Cas endonuclease introduces a double strand break in the test gene;
• deleting all or a portion of the test gene to decrease expression of the test gene;
• co-culturing the target cell having decreased expression of the test gene with an effector cell;
• co-culturing a negative control cell with the effector cell, wherein the negative control cell is identical to the target cell except that it does not comprise the nucleic acid encoding a Cas endonuclease and the nucleic acid encoding a single guide RNA (sgRNA) molecule and does not have decreased expression of the test gene;
• measuring a level of lysis of the target cell by the effector cell;
• measuring a level of lysis of the negative control cell by the effector cell;
• and
• comparing the level of lysis of the target cell to the level of lysis of the negative control cell;
• wherein a decrease in the level of lysis of the target cell as compared to the level of lysis of the negative control cell indicates that mutation of the test gene confers resistance to T cell-mediated cytolytic activity to the target cell;
• and
• wherein a lack of a decrease in the level of lysis of the target cell as compared to the level of lysis of the negative control cell indicates that mutation of the test gene does not confer resistance to T cell-mediated cytolytic activity to the target cell.