Avid Bioservices Inc (CDMO): 12-11-08: Dr. Brekken presents Fully-Hum...

Reply Private New

Next 10 Prev Next

Send PM Follow Ignore

Followers	72
Posts	4827
Boards Moderated	0
Alias Born	01/24/2004

cjgaddy

Re: None

Thursday, 12/11/2008 10:58:09 PM

Thursday, December 11, 2008 10:58:09 PM

12-11-08: Dr. Brekken presents Fully-Human 2C3 (PGN311) at SanAntonio Breast-Cancer Conf.

Dec10-13 2008: “31st San Antonio Breast Cancer Symposium” (SABCS)
“An intl. scientific symposium for interaction & exchange among basic scientists & clinicians in breast cancer”
http://www.sabcs.org . . .Abstracts: http://www.sabcs.org/EnduringMaterials/Index.asp#abstracts

Poster Session I: Tumor Cell & Molecular Biology: Angiogenesis (Dec11 5:00-7:00pm)
12-11-08 5-7pm, poster #1034:
“Selective Inhibition Of VEGFR2 Activity with a Human Anti-VEGF Monoclonal Antibody Decreases Tumor Growth & Macrophage Infiltration in an Orthotopic Model of Breast Cancer” [Fully-Human 2C3 = R84 = PGN311 (Affitech)]
Dineen SP, Lynn KD, Roland CL, Payton LA, Brekken RA [PPHM SRB] - UTSW-MC/Dallas
ABSTRACT:
In general tumor associated macrophages confer a negative prognosis in patients with breast cancer. This is due in part to the fact that macrophages can promote angiogenesis and mediate the angiogenic switch in tumors. Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis as well as a macrophage chemotactic protein. Inhibition of VEGF is an attractive therapeutic strategy that has shown to be beneficial in combination with chemotherapy for some breast cancer patients. However, the mechanism by which inhibition of VEGF affects tumor growth appears to involve more than its effect on endothelial cells. We have previously shown that 2C3 (PGN-310), a mouse monoclonal antibody that prevents VEGF from binding to VEGF receptor 2, decreases tumor growth, angiogenesis, and macrophage infiltration into pancreatic tumors. In this study, we test a fully human version of 2C3, termed r84 (PGN-311), for its effect on established orthotopic MDA-MB-231 breast tumors in SCID mice. Orthotopic tumors were established by injecting one million MDA-MB-231 cells into the mammary fat pad of SCID mice. Therapy with saline (n=5), bevacizumab (n=8), 2C3 (n=5), or r84 (n=9) at 250 g/ip injection twice weekly was initiated on day 26 post tumor cell injection (mean initial tumor volume = 150 mm3) and continued for approx. 3 weeks. Upon sacrifice, tumor weight was determined and the tumor and other organs were snap frozen or fixed in formalin and paraffin-embedded for histology. Anti-VEGF therapy inhibited growth of orthotopic breast tumors (on day 48, Mean SEM: control, 822 160; bevacizumab, 344 29; 2C3, 309 69; r84, 368 38 mm3;all p < 0.001 vs control). Furthermore, immunohistochemical analysis of tumors from control and anti-VEGF treated animals demonstrated that each anti-VEGF therapy reduced microvessel density and macrophage infiltration. Additionally, we also determined that inhibition of VEGF activity with 2C3 reduces VEGF-induced migration of MDA-MB-231 cells in vitro in a transwell assay.
In summary, we demonstrate that r84, a unique fully human anti-VEGF antibody, is effective in reducing tumor microvessel density, macrophage infiltration into tumors, and the growth of breast tumors implanted into SCID mice. These data suggest that inhibition of VEGF receptor 2 activity with an anti-VEGF monoclonal antibody is sufficient for effective blockade of the pro-tumorigenic activities of VEGF.
http://www.abstracts2view.com/sabcs/view.php?nu=SABCS08L_1192

= = = = = = = = = =
ANTI-ANGIOGENESIS AGENT ’2C3’ (ANTI-VEGF MAB):
11-3-07: Dr. Brekken (PPHM SRB) presents ‘R84’ (fully-human 2C3, aka PGN311) data at IBC-Conf: http://tinyurl.com/yp459d
“R84 is a fully human Anti-VEGF mab that selectively blocks VEGF from binding only to REC2… potential advantages over non-selective approaches like Avastin… we are initiating addl preclinical studies to advance R84 as our next potential clinical candidate."

4-16-07 AACR2007: Brekken [PPHM SRB] presents fully-human 2C3 (‘R3’) http://tinyurl.com/2udkgr
”The anti-tumor activity of 2C3, which only blocks VEGFR2 compared favorably to that of Avastin, which blocks VEGF binding to both VEGFR1 & VEGFR2”

2-14-05: Humanized 2C3 Pre-Clin. Data Presented at "Anti-Angio. Agents Symposium": http://tinyurl.com/85qy3
"2C3 shows potent anti-tumor activity in a variety of solid tumors including an 85% reduction in blood vessel formation in breast cancer metastases"

2-10-05: VEGF Pioneer Dr. Donald Senger joins PPHM’s SRB to assist with 2C3 pgm: http://tinyurl.com/yul72w

5-20-03: PPHM compares 2C3 vs. Genentech’s AVASTIN: http://tinyurl.com/37k2nl

= = = = = = = = =
Peregrine webpage on 2C3:
http://www.peregrineinc.com/index.php?option=com_content&task=view&id=33&Itemid=48

PPHM’s SRB – ONCOLOGY (8 scientists total, see http://tinyurl.com/2cy3cv):
Rolf A. Brekken, Ph.D. - Assistant Professor of Surgery, Univ. of Texas SW Medical Center at Dallas
http://utsouthwestern.edu/findfac/research/0,2357,10808,00.html
PMeds: http://tinyurl.com/yuxsp9