2. Academic Validation
  3. Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma

Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma

  • Leukemia. 2010 Sep;24(9):1566-73. doi: 10.1038/leu.2010.141.
A G Polson 1,  M Williams,  A M Gray,  R N Fuji,  K A Poon,  J McBride,  H Raab,  T Januario,  M Go,  J Lau,  S-F Yu,  C Du,  F Fuh,  C Tan,  Y Wu,  W-C Liang,  S Prabhu,  J-P Stephan,  J-A Hongo,  R C Dere,  R Deng,  M Cullen,  R de Tute,  F Bennett,  A Rawstron,  A Jack,  A Ebens
Affiliations

Affiliation

  • 1 Research and Early Development, Genentech, South San Francisco, CA 94080, USA. polson@gene.com
PMID: 20596033 DOI: 10.1038/leu.2010.141
Abstract

Antibody-drug conjugates (ADCs) are potent cytotoxic drugs linked to Antibodies through chemical linkers, and allow specific targeting of drugs to neoplastic cells. The expression of CD22 is limited to B-cells, and we show that CD22 is expressed on the vast majority of non-Hodgkin's lymphomas (NHLs). An ideal target for an ADC for the treatment of NHL would have limited expression outside the B-cell compartment and be highly effective against NHL. We generated an ADC consisting of a humanized anti-CD22 antibody conjugated to the anti-mitotic agent maytansine with a stable linker (anti-CD22-MCC-DM1). Anti-CD22-MCC-DM1 was broadly effective in in vitro killing assays on NHL B-cell lines. We did not find a strong correlation between in vitro potency and CD22 surface expression, internalization of ADC or sensitivity to free drug. We show that anti-CD22-MCC-DM1 was capable of inducing complete tumor regression in NHL xenograft mouse models. Further, anti-CD22-MCC-DM1 was well tolerated in cynomolgus monkeys and substantially decreased circulating B-cells as well as follicle size and germinal center formation in lymphoid organs. These results suggest that anti-CD22-MCC-DM1 has an efficacy, safety and pharmacodynamic profile that support its use as a treatment for NHL.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-132251
    ADC Linker