Poster Display session Poster Display session

81P - Optimizing novel anti-4-1BB antibodies on a in vivo drug screening platform (ID 446)

Presentation Number
81P
Lecture Time
12:30 - 12:30
Speakers
  • Y. Yang (Beijing, China)
Session Name
Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2018
Time
12:30 - 13:00
Authors
  • Y. Yang (Beijing, China)
  • Y. Guo (Beijing北京, China)
  • Y. Shen (Beijing北京, China)
  • J. Ni (Beijing, China)

Abstract

Background

4-1BB, also called TNF receptor super family member 9 or CD137, is mainly expressed on the surface of activated T, NK, and mononuclear cells. 4-1BB is activated by its ligand 4-1BBL or an activating 4-1BB monoclonal antibody, and stimulates T cell activation, proliferation and cytokine production. This co-stimulatory signal can also multiply antigen presenting cells and result in enhanced cell factor secretion. Experiments show that 4-1BB co-stimulation regulates T cell and antigen presenting cell function for antitumor immunity, providing new targets for tumor immunological therapies.

Methods

Here, we developed a cohort of 4-1BB specific antibodies using the classic hybridoma technology. Then, we utilized humanized 4-1BB mice (B-h-4-1BB) and implanted syngeneic tumors subcutaneously, followed by treating mice with purified testing antibodies. Via this approach, we are able to discern several clones that effectively inhibited tumor growth without prior knowledge of their in vitro activities. These clones were further selected for humanization. The cohort of recombinant humanized 4-1BB antibodies were screened in B-h4-1BB mice.

Results

A cohort of 4-1BB specific antibodies were successfully generated and purified. These purified antibodies were screened by their efficacy to stimulate anti-tumor activity in live animals using Biocytogen’s humanized mouse platform. Top clones were humanized and screened by using B-h4-1BB mice. Both the Fv and Fc portion of the lead antibody were optimized using the B-h4-1BB mice, leading to the humanized form of the antibodies.

Conclusions

We adopted an in vivo screen approach to discover candidates of 4-1BB specific antibodies that have potent anti-tumor activity. We discovered the leads with the most potent anti-tumor activity.

Legal entity responsible for the study

Biocytogen Boston Corp.

Funding

Biocytogen Boston Corp.

Disclosure

All authors have declared no conflicts of interest.

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