Anti‐JAM‐C therapy eliminates tumor engraftment in a xenograft model of mantle cell lymphoma

Targeting JAM‐C in a MCL mouse model reduced B cell proliferation and prevented lymphoma B cells from reaching supportive lymphoid microenvironments. Junctional adhesion molecule (JAM)‐C is a member of the JAM family, expressed by a variety of different cell types, including human B lymphocytes and some B‐cell lymphoma subtypes—in particular, mantle cell lymphoma (MCL). Treatment with anti‐JAM‐C pAbs reduces homing of human B cells to lymphoid organs in a NOD/SCID mouse model. In the present study, the role of JAM‐C in the engraftment of human lymphoma B cells in mice was investigated. Administration of novel anti‐JAM‐C mAbs reduced tumor growth of JAM‐C+ MCL cells in bone marrow, spleen, liver, and lymph nodes of mice. Treatment with anti‐JAM‐C antibodies significantly reduced the proliferation of JAM‐C‐expressing lymphoma B cells. Moreover, the binding of anti‐JAM‐C antibodies inhibited the phosphorylation of ERK1/2, without affecting other signaling pathways. The results identify for the first time the intracellular MAPK cascade as the JAM‐C‐driven signaling pathway in JAM‐C+ B cells. Targeting JAM‐C could constitute a new therapeutic strategy reducing lymphoma B‐cell proliferation and their capacity to reach supportive lymphoid microenvironments.