Using computational chemistry and a suite of ex vivo lymphocyte assays, we identified allosteric domains of ITK and BTK and developed molecular probes to specifically and functionally modulate their activities. These pro-drugs heighten activated states of lymphocytes in vivo when T and B cell antigen receptors are triggered and thereby generate superior T and B cells across the functional spectrum. Precision drugs in development are predicted to replenish patients with T and B lymphocytes with greater fitness to eliminate cancer cells and restore systemic normalcy in various immune mediated diseases.