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Immunology 2018
J u l y 0 5 - 0 7 , 2 0 1 8
V i e n n a , A u s t r i a
Page 35
Journal of Clinical Immunology and Allergy
ISSN 2471-304X
1 5
t h
I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology
Breast cancer (BC) is the most diagnosed malignancy and the second cause
of cancer death in women in the United States. It is estimated that 252,710
new cases of BC will be diagnosed in 2017 and 40,610 women are projected
to die from breast cancer in the US. Human epidermal growth factor receptor
HER2/neu
overexpression is found in 25-30% of human BCs and correlates
with high aggression, high risk of relapse, high rate of metastasis, and poor
survival. We have developed novel nano immune conjugate (NIC) versions with
single conjugated anti-mouse CTLA-4 mAb (a-msCTLA-4) and anti-PD-1mAb
(a-PD-1). The NIC activities were tested in BALB/c mice bearing subcutaneous
(sc) syngeneic murine mammary carcinoma cells D2F2. This cell line is the
parental line of the D2F2/E2 that expresses human HER2. Tumor growth
was significantly inhibited when treated with NIC’s containing a-CTLA-4 and
tumour targeting anti-mouse TfR mAb (a-msTfR) compared to free a-CTLA-4.
Inhibition was accompanied by reduced levels of CD4+FOXP3+ Tregs that are
also targets of a-CTLA-4. Anti-PD-1 treatment was performed with animals
carrying primary HER2+ D2F2/E2 sc tumours using the NIC P/a-msTfR/a-
PD-1. Serum cytokine IL10, and especially IL-12, were significantly enhanced
in comparison with treatment of a-pD-1 alone, and increased further during
treatment with NIC P/a-msTfR/a-PD-1/AON c-Myc. In all cases, size of sc
D2F2/E2 breast cancer was significantly reduced. The expression of IL-12 and
IL-10 was also induced in mouse sera treated with free a-pD-1. Interestingly,
NIC with AON to c-Myc induced higher cytokine expression. It is expected that
a much stronger anti-tumour activity is observed for co-administration and/or
codelivery of the antibodies and antisense drugs.
Conclusion:
Treatment of HER2 breast cancer with nano immune conjugates
increased significantly client survival.
Biography
Eggehard Holler, PhD, is Professor of Neurosurgery
and Biomedical Sciences, and Director of Syntheses at
Nanomedicine Research Centre, Department of Neurosurgery,
Cedars-Sinai Medical Centre, Los Angeles, USA. He has
completed his PhD from University of Regensburg, DE and has
Postdoctoral appointments at Cornell and Berkeley. He was
Professor of Biochemistry at University of Regensburg until
2005, and since 2008, he is Research Scientist and Professor
at Cedars-Sinai Medical Centre, USA. He has served at several
international universities as Visiting Professor, published more
than 150 papers and was Interims Director of Institute of
Biophysical Chemistry at Regensburg
.
Eggehard.holler@cshs.orgMacromolecular nano immunoconjugates targeting checkpoint
inhibitors CTLA-4 and PD-1 for treatment of breast cancer
Eggehard Holler
1,2
, Anna Galstyan
1
, Antonella Chiechi
1
,
Alexander V Ljubimov
1
, Tao Sun
1
, Ekaterina Shatalova
1
, Keith L
Black
1
, Hui Ding
1
and Julia Y Ljubimova
1
1
Cedars-Sinai Medical Center, USA
2
Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, Germany
Eggehard Holler et al., Insights Allergy Asthma Bronchitis 2018, Volume: 4
DOI: 10.21767/2471-304X-C1-002