By using Cas9 to disrupt CAR T cells, immune checkpoints such as PD-1 could overcome the major challenge of checkpoint inhibition in tumor cells [47] To reduce the alloreactivity, multiplex CRISPR CAR T cells being used as an anti-tumor agent by blocking PD1 inhibitory pathway with excision of TCR, B2M, and PD1 in T cells as a potential leukemic tumor treating model. The gene discussed is B2M; the disease is neoplasm.