Saturday, April 13, 2013 3:25:13 PM
Sunday, May 5th in Honolulu. Hawaii.
http://www.immunology2013.org/index.html
CURRENT ABSTRACT TOPIC CATEGORY: Immunotherapy and Vaccines
TITLE: Combined targeting of exposed phosphatidylserine, CD47 and CD54 on
human pancreatic tumor cells in a mouse xenograft model of human pancreatic cancer
(P4455)
AUTHORS (FIRST NAME, LAST NAME): Shihong Ma 1, 2, Philip Thorpe 3, Ellen
S. Vitetta 2, 4, 5, Jeffrey Meyer 1
INSTITUTIONS (ALL): 1. Department of Radiation Oncology, UT Southwestern
Med. Ctr., Dallas, TX, United States.
2. Cancer Immunobiology Center, UT Southwestern Med. Ctr., Dallas, TX, United
States.
3. Department of Pharmacology, UT Southwestern Med. Ctr., Dallas, TX, United
States.
4. Department of Microbiology, UT Southwestern Med. Ctr., Dallas, TX, United
States.
5. Department of Immunology, UT Southwestern Med. Ctr., Dallas, TX, United
States.
ABSTRACT BODY: Phosphatidylserine (PS) is normally intracellular but becomes
exposed on the luminal surface of vascular endothelium in tumors and can also be
expressed on tumor cells themselves. Studies have shown that targeting PS with an
antibody enhances the antitumor effect of chemotherapy or radiation on several
tumors, and induces antitumor immunity in mice. Combination of this anti-vascular and
antitumor antibody with an antibody (anti-CD47) that blocks the “don’t eat me” signal
CD47 commonly expressed on human tumors may lead to synergistic antitumor
activity. Similarly, synergistic antitumor activity might be obtained by combining the
PS-targeting antibody with anti-CD54, an antibody that has been demonstrated to have
pan antitumor activity in xenograft models and is safe in humans. Our objective is to
evaluate combinations of these antibodies in a xenograft model of human cancer.
Studying these combinations requires determining the expression of CD47 and CD54
on several cancer cell lines. To this end, MDA-MB-231 (breast), NCI-H157 (lung),
Du145 (prostate), PANC-1 and BxPC-3 (pancreatic) were analyzed for surface
expression of CD47 and CD54. All five cell lines expressed CD47 (>87% of cells
positive). All tested cell lines were also highly CD54 positive (>84% of cells positive)
except for MDA-MB-231 (~50% positive). The effects of anti-PS antibody in
conjunction with anti-CD47 or anti-CD54 on tumor growth are currently being
analyzed in SCID mice bearing BxPC-3 pancreatic tumors.
Funding Support: Supported by the Horchow Foundation, the department of
Radiation Oncology and the Cancer Immunobiology Center, UT Southwestern Medical Center
CONTROL ID: 1641664
PRESENTATION TYPE: Oral and Poster
"By all means let's be open-minded, but not so open-minded that our brains drop out." - Richard Dawkins
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