mAbs, vaccines, IMiDs, checkpoint inhibitors, CARTs and TCRs bear great theurapeutic potential to overcome effects of immune suppressive cytokines and accessory cells in the BM microenvironment, restore host CD4, CD8, and NK cell anti-tumor immunity, and improve patient outcome in MM and with their acceptable toxicity profiles are prime candidates for not only the treatment on relapsed refractory patients but also in newly diagnosed and even in preclinical disease. The gene discussed is CD4; the disease is neoplasm.