Bispecifics
Published on February 22, 2024
Antibody-based human immunotherapies in syngeneic mouse model
by Blood Advances
Albring JC, Frebel K, Wohlgemuth A, et al. Comparison of Antibody-Based Immunotherapeutics for Malignant Hematological Disease in an Experimental Murine Model. Blood Advances. 2024; (doi: 10.1182/bloodadvances.2023011647).
Scientists have developed a syngeneic mouse model that accurately reflects antitumor activity and adverse effects detected following different types of antibody-based human immunotherapy. The model allows for direct comparisons of safety and efficacy in three interventions — all of which target the Slamf7 immune receptor that is naturally expressed in MPC-11, a multiple myeloma cell line observed in mice. Bispecific T cell engagers (Slamf7-BiTE) and chimeric antigen receptor T cells (Slamf7-CART) effectively killed MPC-11 cells in vitro. The third immunotherapy, monoclonal antibodies (Slamf7-mAb), triggered antigen-specific antibody-dependent cellular toxicity. All three treatments demonstrated anti-tumor function against Slamf7-expressing targets in vivo. Slamf7-CART — and to a lesser degree, Slamf7-BiTE — were associated with weight loss, general malaise, and other side effects in test animals. Both of those immunotherapies also maintained activity in allogeneic transplant vs. the non-transplant setting, but Slamf7-mAb aggressively engaged in anti-myeloma behavior. Researchers say the experimental model can contribute to the development and advancement of immunotherapies and help inform new strategies to minimize unfavorable effects after stem cell transplantation.
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