Abstract 5717
Background
We have generated a therapeutic anti-PD-L1/IL-15 fusion protein (KD033) by combining a proprietary, fully human, high affinity anti-PD-L1 antibody with human IL-15. We have also generated a surrogate KD033 by combining an anti-mouse PD-L1 surrogate antibody with human IL-15. Both KD033 and KD033 surrogate significantly increased CD8+ T, NK and NKT cells in peripheral blood in monkeys and mice respectively. KD033 surrogate treatment resulted in tumor clearance and generated memory responses in syngeneic mouse models of colon carcinoma. We examined the extent of memory responses in these KD033 surrogate-treated tumor-free mice and evaluated the molecular mechanisms of KD033 surrogate efficacy.
Methods
Mouse CT26 colon carcinoma cells were grown subcutaneously in Balb/c mice prior to intravenous treatments with fusion proteins. Tumor-free mice were re-challenged with tumors from the same genetic background. For immune gene expression analysis, tumors were isolated 7 days after treatments and analyzed using the mouse PanCancer IO 360 Gene Expression Panel from Nanostring.
Results
KD033 surrogate treatment was associated with increased cytotoxic lymphocyte infiltrations in tumors and the microenvironment. One hundred percent (100%) of KD033 surrogate-treated tumor-free animals rejected the same tumor without any additional treatments. Mice re-challenged with unrelated tumors from the same background were rejected or demonstrated reduction of tumor growth without further treatments. KD033 surrogate-treated tumors showed significant increases in expression of genes involved in cytokine, adaptive and inflammatory pathways and upregulation of immune gene signatures involving not only cytotoxic cells but also dendritic and B cells.
Conclusions
KD033 surrogate inhibited tumor growth inhibition and demonstrated evidence of epitope spreading. Broad activation of innate and adaptive immune responses in tumors was observed. These observations strongly support KD033 clinical development. A phase I clinical trial of KD033 is planned in 2H 2019.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Animal studies were conducted for Kadmon by Crown Bioscience Inc. with approved SOP and IACUC protocol. Nanostring platform analysis was done for Kadmon by Canopy Biosciences.
Funding
Kadmon Corporation, LLC.
Disclosure
S. Martomo: Full / Part-time employment: Kadmon Corporation. X. Feng: 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. M.V. Poyurovsky: Full / Part-time employment: Kadmon Corporation. K. McCracken: Full / Part-time employment: Kadmon Corporation. F. Miyara: Full / Part-time employment: Kadmon Corporation. L. Li: Full / Part-time employment: Kadmon Corporation. S. Aggarwal: Full / Part-time employment: Kadmon Corporation. J. Patel: Full / Part-time employment: Kadmon Corporation.
Resources from the same session
5520 - Patient’s Usability Test results of a CINV Diary Application For Smartphones
Presenter: Paz Fernandez
Session: Poster Display session 3
Resources:
Abstract
2323 - Colorectal Telephone Assessment Pathway (CTAP) - A viable means of shortening time to a definitive diagnosis of Colorectal Cancer (CRC)
Presenter: Harriet Watson
Session: Poster Display session 3
Resources:
Abstract
6119 - Cancer Nursing and Social Media: Capturing the Zeitgeist
Presenter: Mark Foulkes
Session: Poster Display session 3
Resources:
Abstract
1776 - Examination of mobile applications on breast cancer
Presenter: AYDANUR AYDIN
Session: Poster Display session 3
Resources:
Abstract
4128 - E-health effectiveness to increase patient adherence for immunotherapy; a cost-benefit study.
Presenter: Maria José Dias
Session: Poster Display session 3
Resources:
Abstract
3219 - Experiences of internet-based stepped care among individuals with recently diagnosed cancer and symptoms of anxiety and/or depression
Presenter: Anna Hauffman
Session: Poster Display session 3
Resources:
Abstract
5010 - What do cancer patients know about their immunotherapy treatment?
Presenter: Mónica Arellano
Session: Poster Display session 3
Resources:
Abstract
4503 - Prospective Comparison of Travel Burden, Cost and Time to Obtain Tumor Board Treatment Plan Through In-Person Visits vs. an AI Enabled Health Technology (N=1803)
Presenter: Rajendra Badwe
Session: Poster Display session 3
Resources:
Abstract
4123 - Cancer care through the fire and flames: 3-year experience in the utilisation of electronic consultation and referral system at the Red Zone in Southern Thailand
Presenter: Nanthiya Rattanakhot
Session: Poster Display session 3
Resources:
Abstract
2087 - The effect of e-mobile education on the quality of life in women with breast cancer
Presenter: Derya ÇInar
Session: Poster Display session 3
Resources:
Abstract