Combination Therapy to Enhance Antibody Dependent Cellular Cytotoxicity

  • Combination therapy that targets nonresponsive malignancies.
  • May treat a wide range of cancers.

Abstract

Technology Description

Anti-cancer monoclonal antibodies (mAbs), including rituximab (anti-CD20) and cetuximab (anti-EGFR), are a standard component of cancer therapy. A major mechanism of action of anti-cancer mAbs is NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Resistance to mAb therapy remains a clinical challenge. Inventors at the University of Iowa have previously demonstrated that T cells, mediated largely by interleukin-2 (IL-2) locally produced by CD4+ T cells, help maintain long-term NK cell-mediated ADCC and NK number. Thus, lack of adequate T cell help may explain some cases of resistance to mAb therapy.

The inventors have developed a combination therapy to enhance the efficacy of mAb and help treat resistant and recurrent malignancies. Activation of T cells by anti-CD3 x anti-cancer bispecific antibodies in the presence of cancer significantly enhances the ability of T cells to support NK cell viability, and this, in turn enhances ADCC. Enhanced ADCC mediated by anti-CD3 x anti-cancer bispecific antibody is seen with very small numbers of T cells, very low concentrations of bispecific antibody and short exposure to bispecific antibody. Therefore, intermittent therapy with a bispecific antibody, given along with mAb could result in improved therapeutic effectiveness of both agents.

UIRF Case No. 2021-069

Stage of Development

The effectiveness of the combination therapy has been tested in vitro and a clinical trial is expected to open shortly to further test the effects of short-term systemic bispecific antibody treatment on the efficacy of anti-tumor mAb.

Website

https://uiowa.flintbox.com/technologies/5F12F47EF7CA4C3CA0E5632C888C28A3

Advantages

  • Novel combination
  • Treats recurrent malignancies and those that do not respond to traditional mAb therapy
  • Can be used to treat a wide variety of cancers

Contact Information

Name: Mihaela D. Bojin

Email: mihaela-bojin@uiowa.edu

Phone: 319-335-2723