HER2 Support Group Forums - View Single Post - Scientists Develop New Therapy For HER2-Positive Breast Cancer

Jackie07 · 07-26-2011, 11:35 PM

Great news! The concept was reported less than two years ago. Looks like they are making good progress. [See also Lani's thread: http://her2support.org/vbulletin/sho...ight=Affitoxin ]

J Immunother. 2009 Oct;32(8):817-25.
Affitoxin--a novel recombinant, HER2-specific, anticancer agent for targeted therapy of HER2-positive tumors.

Zielinski R, Lyakhov I, Jacobs A, Chertov O, Kramer-Marek G, Francella N, Stephen A, Fisher R, Blumenthal R, Capala J.
Source

Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in 25% to 30% of breast cancers and has been associated with an unfavorable prognosis. Here we report the construction, purification, and characterization of Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2-specific Affibody molecule as a targeting moiety and PE38KDEL, which is a truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is highly soluble and does not require additional refolding, oxidation, or reduction steps during its purification.

Using surface plasmon resonance technology and competitive binding assays, we have shown that Affitoxin binds specifically to HER2 with nanomolar affinity. We have also observed a high correlation between HER2 expression and retention of Affitoxin bound to the cell surface. Affitoxin binding and internalization is followed by Pseudomonas exotoxin A activity domain-mediated ADP-ribosylation of translation elongation factor 2 and, consequently, inhibition of protein synthesis as shown by protein expression analysis of HER2-positive cells treated with Affitoxin. Measured IC50 value for HER2-negative cells MDA-MB468 (65+/-2.63 pM) was more than 20 times higher than the value for low HER2 level-expressing MCF7 cells (2.56+/-0.1 pM), and almost 3 orders of magnitude higher for its HER2-overexpressing derivative MCF7/HER2 (62.7+/-5.9 fM).

These studies suggest that Affitoxin is an attractive PE38-based candidate for treatment of HER2-positive tumors.

07-26-2011, 11:35 PM	#4
Jackie07 Senior Member Join Date: Jan 2008 Location: "Love never fails." Posts: 5,808	Re: Scientists Develop New Therapy For HER2-Positive Breast Cancer Great news! The concept was reported less than two years ago. Looks like they are making good progress. [See also Lani's thread: http://her2support.org/vbulletin/sho...ight=Affitoxin ] J Immunother. 2009 Oct;32(8):817-25. Affitoxin--a novel recombinant, HER2-specific, anticancer agent for targeted therapy of HER2-positive tumors. Zielinski R, Lyakhov I, Jacobs A, Chertov O, Kramer-Marek G, Francella N, Stephen A, Fisher R, Blumenthal R, Capala J. Source Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Abstract Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in 25% to 30% of breast cancers and has been associated with an unfavorable prognosis. Here we report the construction, purification, and characterization of Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2-specific Affibody molecule as a targeting moiety and PE38KDEL, which is a truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is highly soluble and does not require additional refolding, oxidation, or reduction steps during its purification. Using surface plasmon resonance technology and competitive binding assays, we have shown that Affitoxin binds specifically to HER2 with nanomolar affinity. We have also observed a high correlation between HER2 expression and retention of Affitoxin bound to the cell surface. Affitoxin binding and internalization is followed by Pseudomonas exotoxin A activity domain-mediated ADP-ribosylation of translation elongation factor 2 and, consequently, inhibition of protein synthesis as shown by protein expression analysis of HER2-positive cells treated with Affitoxin. Measured IC50 value for HER2-negative cells MDA-MB468 (65+/-2.63 pM) was more than 20 times higher than the value for low HER2 level-expressing MCF7 cells (2.56+/-0.1 pM), and almost 3 orders of magnitude higher for its HER2-overexpressing derivative MCF7/HER2 (62.7+/-5.9 fM). These studies suggest that Affitoxin is an attractive PE38-based candidate for treatment of HER2-positive tumors. __________________ Jackie07 http://www.kevinmd.com/blog/2011/06/doctors-letter-patient-newly-diagnosed-cancer.html http://www.asco.org/ASCOv2/MultiMedi...=114&trackID=2 NICU 4.4 LB Erythema Nodosum 85 Life-long Central Neurocytoma 4x5x6.5 cm 23 hrs 62090 semi-coma 10 d PT OT ST 30 d 3 Infertility tmts 99 > 3 u. fibroids > Pills CN 3 GKRS 52301 IDC 1.2 cm Her2 +++ ER 5% R. Lmptmy SLNB+1 71703 6 FEC 33 R Tamoxifen Recc IIB 2.5 cm Bi-L Mast 61407 2/9 nds PET 6 TCH Cellulitis - Lymphedema - compression sleeve & glove H w x 4 MUGA 51 D, J 49 M Diastasis recti Tamoxifen B. scan Irrtbl bowel 1'09 Colonoscopy 313 BRCA1 V1247I hptc hemangioma Vertigo GI - > yogurt hysterectomy/oophorectomy 011410 Exemestane 25 mg tab 102912 ~ 101016 stopped due to r. hip/l.thigh pain after long walk DEXA 1/13 1-2016 lesions in liver largest 9mm & 1.3 cm onco. says not cancer. 3-11 Appendectomy - visually O.K., a lot of puss. Final path result - not cancer. Start Vitamin D3 and Calcium supplement （600mg x2) 10-10 Stopped Exemestane due to r. hip/l.thigh pain OKed by Onco 11-08-2016 7-23-2018 9 mm groundglass nodule within the right lower lobe with indolent behavior. Due to possible adenocarcinoma, Recommend annual surveilence. 7-10-2019 CT to check lung nodule. 1-10-2020 8mm stable nodule on R Lung, two 6mm new ones on L Lung, a possible lymph node involvement in inter fissule. "I WANT TO BE AN OUTRAGEOUS OLD WOMAN WHO NEVER GETS CALLED AN OLD LADY. I WANT TO GET SHARP EDGED & EARTH COLORED, TILL I FADE AWAY FROM PURE JOY." Irene from Tampa Advocacy is a passion .. not a pastime - Joe Last edited by Jackie07; 07-28-2011 at 06:31 PM..