| First Author | Meermeier EW | Year | 2021 |
| Journal | Blood Cancer Discov | Volume | 2 |
| Issue | 4 | Pages | 354-369 |
| PubMed ID | 34258584 | Mgi Jnum | J:308274 |
| Mgi Id | MGI:6728633 | Doi | 10.1158/2643-3230.bcd-21-0038 |
| Citation | Meermeier EW, et al. (2021) Tumor burden limits bispecific antibody efficacy through T cell exhaustion averted by concurrent cytotoxic therapy. Blood Cancer Discov 2(4):354-369 |
| abstractText | BCMA-CD3-targeting bispecific antibodies (BsAb) are a recently developed immunotherapy class which shows potent tumor killing activity in multiple myeloma (MM). Here, we investigated a murine BCMA-CD3-targeting BsAb in the immunocompetent Vk*MYC and its IMiD-sensitive derivative Vk*MYC(hCRBN) models of MM. The BCMA-CD3 BsAb was safe and efficacious in a subset of mice, but failed in those with high-tumor burden, consistent with clinical reports of BsAb in leukemia. The combination of BCMA-CD3 BsAb with pomalidomide expanded lytic T cells and improved activity even in IMiD resistant high-tumor burden cases. Yet, survival was only marginally extended due to acute toxicity and T cell exhaustion, which impaired T cell persistence. In contrast, the combination with cyclophosphamide was safe and allowed for a tempered pro-inflammatory response associated with long-lasting complete remission. Concurrent cytotoxic therapy with BsAb actually improved T cell persistence and function, offering a promising approach to patients with a large tumor burden. |
