| Autor: |
Andrew G. Polson, Peter S. Dragovich, Jack D. Sadowsky, Thomas Pillow, Melissa M. Schutten, Rebecca K. Rowntree, Peter Yan, Kyu Hong, Montserrat Carrasco-Triguero, Fiona Zhong, Helen Booler, Douglas Leipold, Geoffrey del Rosario, Bing Zheng, Donna W. Lee, Shang-Fan Yu |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1535-7163.c.6542727.v1 |
| Popis: |
We are interested in developing a second generation of antibody–drug conjugates (ADCs) for the treatment of non-Hodgkin lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule-inhibiting ADCs pinatuzumab vedotin [anti–CD22-vc-monomethyl auristatin E (MMAE)] and polatuzumab vedotin (anti–CD79b-vc-MMAE). Pinatuzumab vedotin (anti–CD22-vc-MMAE) and polatuzumab vedotin (anti–CD79b-vc-MMAE) are ADCs that contain the microtubule inhibitor MMAE. Clinical trial data suggest that these ADCs have promising efficacy for the treatment of NHL; however, some patients do not respond or become resistant to the ADCs. We tested an anti-CD22 ADC with a seco-CBI-dimer payload, thio-Hu anti–CD22-(LC:K149C)-SN36248, and compared it with pinatuzumab vedotin for its efficacy and duration of response in xenograft models and its ability to deplete normal B cells in cynomolgus monkeys. We found that anti–CD22-(LC:K149C)-SN36248 was effective in xenograft models resistant to pinatuzumab vedotin, gave a longer duration of response, had a different mechanism of resistance, and was able to deplete normal B cells better than pinatuzumab vedotin. These studies provide evidence that anti–CD22-(LC:K149C)-SN36248 has the potential for longer duration of response and more efficacy in indolent NHL than MMAE ADCs and may provide the opportunity to improve outcomes for patients with NHL. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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