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
5579 - Quality of informed consent in clinical trials patients
Presenter: Gianluca Catania
Session: Poster Display session 3
Resources:
Abstract
5147 - Patient's rights: Where do we stand?
Presenter: Maja Kozuh
Session: Poster Display session 3
Resources:
Abstract
1279 - The oncology nurse coordinator’s role in a digestive oncology department: Impact on patient and hospital
Presenter: Fouad Awada
Session: Poster Display session 3
Resources:
Abstract
1670 - Nursing model for a breast cancer unit at the Catalan Institute of Oncology
Presenter: Ana Rodriguez-ortega
Session: Poster Display session 3
Resources:
Abstract
3936 - Role of cancer nurse in the prevention and control of acute deterioration for oncohematologic patient
Presenter: Raquel Azor Portolés
Session: Poster Display session 3
Resources:
Abstract
2789 - Standardized nursing care in the department of radiotherapy of a network of cancer centres
Presenter: José Delgado
Session: Poster Display session 3
Resources:
Abstract
4482 - Exploring anxiety, depression and quality of life of ambulatory cancer patients during chemotherapy.
Presenter: Theodoula Adamakidou
Session: Poster Display session 3
Resources:
Abstract
3075 - Implementing a Cancer Survivorship Program for Individuals with Recurrent Breast Cancer
Presenter: Darcy Burbage
Session: Poster Display session 3
Resources:
Abstract
3869 - The perceptions of parents/guardians regarding their child/adolescent’s experience of reflexology or non-specific foot massage The perceptions of parents/guardians regarding their child/adolescents experience of reflexology or non-specific foot massage
Presenter: Patricia Fox
Session: Poster Display session 3
Resources:
Abstract
4064 - Quality of life in survivors of adult haematological malignancies
Presenter: Anita Immanuel
Session: Poster Display session 3
Resources:
Abstract