Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Lunch & Poster Display session

14P - Anti-PDL1/IL-15 fusion protein increases rare effector cells in cynomolgus monkeys and mice

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Stella Martomo

Citation

Annals of Oncology (2019) 30 (suppl_11): xi1-xi11. 10.1093/annonc/mdz447

Authors

S. Martomo1, D. Lu1, Z. Polonskaya1, X. Luna1, F. Miyara2, J. Patel1

Author affiliations

  • 1 Research Department, Kadmon Corporation - Kadmon Holdings, Inc., 10016 - New York/US
  • 2 Business Development Department, Kadmon Corporation - Kadmon Holdings, Inc., 10016 - New York/US
More

Resources

Abstract 14P

Background

Kadmon has generated an anti-PDL1/IL-15 fusion protein (KD033) by combining a proprietary, fully human, high affinity anti-human/mouse PD-L1 antibody with human IL-15. Initial assessment of KD033 showed enhanced tolerability relative to a non-targeted IL-15 fusion protein, in addition to its potent anti-tumor activity and immune memory generation. KD033 increased CD8+ T and NK cells in peripheral blood of humans, cynomolgus monkeys and mice as expected from on target engagement of IL-15. In this study, we evaluated additional immune cell population changes in mice and cynomolgus monkeys treated with KD033.

Methods

Tumor size, measured at day 7 in syngeneic subcutaneous CT26 colorectal cancer mouse model after a single KD033 surrogate treatment, was used to define mice as either KD033 responders (decreasing tumor volumes) or non-responders (no change or increasing tumor volumes). Peripheral blood from KD033 responders and non-responders as well as from cynomolgus monkeys treated with KD033 at predose, 24 and 168 hours after dosing was analyzed by flow cytometry for various immune cell populations.

Results

Granzyme B+ CD8+ T and gamma delta T cells in peripheral blood were specifically increased in KD033 surrogate responder mice. These increases were not observed in non-responder mice. Greater increases in NKT-like cells were also observed in KD033 surrogate best responders. This is in contrast to other immune populations, such as CD8+ T and B cells, which were similarly impacted, in both KD033 surrogate responder and non-responder mice. In cynomolgus monkeys, CD3+CD4-CD8- cells, which includes gamma delta T cells, were one of the immune populations with the highest increases at 168 hours post dose.

Conclusion

KD033 administration increases CD8+ T and NK cells, consistent with IL-15 pharmacodynamics. In addition, analysis of peripheral blood from KD033 surrogate best and non-responder mice demonstrated increases in different immune populations, which can facilitate their use as in-treatment biomarkers of KD033 activity in tumors. Importantly, KD033 administration resulted in increases in rare cytotoxic cells such as NKT and gamma delta T cells in peripheral blood which may contribute to its anti-tumor activity and immunity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Kadmon Corporation LLC.

Funding

Kadmon Corporation LLC.

Disclosure

S. Martomo: Full / Part-time employment: Kadmon Corporation. D. Lu: Full / Part-time employment: Kadmon Corporation. Z. Polonskaya: Full / Part-time employment: Kadmon Corporation. X. Luna: Full / Part-time employment: Kadmon Corporation. F. Miyara: Full / Part-time employment: Kadmon Corporation. J. Patel: Full / Part-time employment: Kadmon Corporation.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings