In vivo therapeutic evaluation of CD37-SMIP. A Raji cell-inoculated xenograft mouse model of disseminated leukemia/lymphoma was used to evaluate the therapeutic efficacy. (A) H&E staining of tissue sections from Raji cell–inoculated SCID mouse (placebo-treated). (i) Thymus infiltrated with neoplastic cells. (ii) Lymphoid atrophy/hypoplasia in spleen. (iii) Extramedullary hematopoiesis in liver (arrows). (iv) Atrophic lymph node partially replaced by tumor cells. (v) Markedly atrophic cervical lymph node. (vi) Spinal nerve showing rare swollen axons (arrow). (vii) Neoplastic cells in meninges over cerebellum. (viii) Neoplastic cells in vertebral bone marrow and within spinal canal. (ix) neoplastic cells in bone marrow. (B) Flow cytometric analysis of bone marrow cells from Raji cells– engrafted mice at day 17 after inoculation. Mice were treated with placebo (saline) or CD37-SMIP, and the percentage of human CD19⁺, human CD20⁺, or human CD37⁺ cells were analyzed by surface staining with PE-labeled antibodies. (C) Depletion of infiltrated human CD45⁺ cells in CD37-SMIP treated but not control mice. Histologic (H&E staining) analysis of thymus (top panels) and lymph node (bottom panels) from control untreated (left panels) or CD37-SMIP–treated (right panels) mice. Insert shows presence of human CD45⁺ cells in the untreated but not in CD37-SMIP–treated mice as detected by immunohistochemistry of the tissue sections. (D) Evaluation of therapeutic efficacy of CD37-SMIP in Raji cell–inoculated SCID mice. Raji cell–inoculated SCID mice were treated with saline (n = 22), negative control trastuzumab (n = 22), rituximab (n = 32), or CD37-SMIP (n = 32). Comparison among different groups was made by log-rank test (P < .001 between CD37-SMIP and trastuzumab, and P = .124 between CD37-SMIP and rituximab).