Articles and methods directed to personalized therapy of cancer

A method of treating lymphoma in a human subject comprising:

• identifying a unique B cell receptor expressed in clonally related malignant lymphoma cells of the subject;
• modifying a population of T cells by introducing nucleic acid molecules encoding the the unique B cell receptor and nucleic acid molecules encoding a library of CARs wherein each CAR within the library comprises extracellular antigen binding domain comprising a distinct putative ligand of a unique B cell receptor, wherein the T cells co-express the unique B cell receptor and a CAR from the library on the cell surface;
• measuring activation of the T cells in response to autocrine CAR signaling induced by binding of the putative ligand of the CAR to the co-expressed unique B cell receptor, thereby identifying a ligand of the unique B cell receptor ligand;
• and
• administering to the subject a therapeutically effective amount of the ligand of the unique B cell receptor coupled to an immunotherapeutic agent, wherein the putative ligand of the unique B cell receptor is a peptide, a cyclopeptide, or a VHH.