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Old 05-12-2011, 08:12 AM   #1
Lani
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Thumbs up exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary needed!

Tiptoe can relax!

Br J Cancer. 2011 May 10. [Epub ahead of print]
A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours.
Borriello M, Laccetti P, Terrazzano G, D'Alessio G, De Lorenzo C.
Source
Dipartimento di Biologia Strutturale e Funzionale, UniversitÃ* Federico II, via Cinthia, Napoli 80126, Italy.
Abstract
Background:ErbB2 is an attractive target for immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumour cells of different origin, with a key role in the development of malignancy. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer with success, can engender cardiotoxicity and a high fraction of patients is resistant to Trastuzumab treatment.Methods:A novel human immunoRNase, called anti-ErbB2 human compact antibody-RNase (Erb-hcAb-RNase), made up of the compact anti-ErbB2 antibody Erbicin-human-compact Antibody (Erb-hcAb) and human pancreatic RNase (HP-RNase), has been designed, expressed in mammalian cell cultures and purified. The immunoRNase was then characterised as an enzymatic protein, and tested for its biological actions in vitro and in vivo on ErbB2-positive tumour cells.Results:Erb-hcAb-RNase retains the enzymatic activity of HP-RNase and specifically binds to ErbB2-positive cells with an affinity comparable with that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumour cells both in vitro and in vivo. Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb.Conclusion:Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours.British Journal of Cancer advance online publication, 10 May 2011; doi:10.1038/bjc.2011.146 www.bjcancer.com.

PMID: 21559015
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Old 05-12-2011, 09:28 AM   #2
chrisy
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Bring it on!!!!
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June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?"
9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response!
04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver
02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1
02/09 Continue NED
02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
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12/11 Begin MM302 Phase I trial - bust:(
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9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
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Old 05-12-2011, 10:05 AM   #3
Ellie F
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Wonder how soon it will be in trials?
Italy here I come!

Ellie
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Old 05-12-2011, 08:44 PM   #4
ElaineM
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Wink Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

I want some of it too.
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Old 05-12-2011, 10:02 PM   #5
Jackie07
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Thanks, Lani. Found an easier-to-read abstract:

British Journal of Cancer , (10 May 2011) | doi:10.1038/bjc.2011.146
A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours
M Borriello, P Laccetti, G Terrazzano, G D'Alessio and C De Lorenzo

Background:

ErbB2 is an attractive target for immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumour cells of different origin, with a key role in the development of malignancy. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer with success, can engender cardiotoxicity and a high fraction of patients is resistant to Trastuzumab treatment.

Methods:

A novel human immunoRNase, called anti-ErbB2 human compact antibody-RNase (Erb-hcAb-RNase), made up of the compact anti-ErbB2 antibody Erbicin-human-compact Antibody (Erb-hcAb) and human pancreatic RNase (HP-RNase), has been designed, expressed in mammalian cell cultures and purified. The immunoRNase was then characterised as an enzymatic protein, and tested for its biological actions in vitro and in vivo on ErbB2-positive tumour cells.

Results:

Erb-hcAb-RNase retains the enzymatic activity of HP-RNase and specifically binds to ErbB2-positive cells with an affinity comparable with that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumour cells both in vitro and in vivo. Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb.

Conclusion:

Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours.
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Last edited by Jackie07; 05-12-2011 at 10:04 PM..
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Old 05-12-2011, 10:22 PM   #6
radiant
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Jackie and/or Lani:

Does ErbB2 mean her2+? I don't understand these acryonmyns.

thx. Kim
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2007 - recurrence to medistinal lymph node, Abraxene and Herceptin - took it down 50%
2008 - on Arimidex/Herceptin - stable lymph node.
2009 - stable on Arimidex/Herceptin
2010 - lymph node progression and liver mets.
2010 - went on Gemzar, Navelbine, Herceptin - Navelbine and Herceptin took liver mets down. lymph node slightly progressed.
2010 - did Xeloda & Tykerb - MAJOR progression in liver in only 6 weeks.
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Old 05-13-2011, 06:44 AM   #7
Jackie07
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Yes, Kim, they are the same thing. See the link below:

http://en.wikipedia.org/wiki/HER2/neu

And thanks for asking. I've noticed that in British publications, ErbB2 is used instead of Her2. Have always thought it's a language difference. Turned out it's more complicated than that.
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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
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Old 05-13-2011, 10:10 AM   #8
radiant
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

wow Jackie - this is GREAT news.
thanks alot!

- Kim
__________________
------------------------------
Dx Stage 3C 2005, triple +, tons of lymph nodes as well. FEC, surgery, TCH, rads, herceptin 1 year. And, Aromasin.
2007 - recurrence to medistinal lymph node, Abraxene and Herceptin - took it down 50%
2008 - on Arimidex/Herceptin - stable lymph node.
2009 - stable on Arimidex/Herceptin
2010 - lymph node progression and liver mets.
2010 - went on Gemzar, Navelbine, Herceptin - Navelbine and Herceptin took liver mets down. lymph node slightly progressed.
2010 - did Xeloda & Tykerb - MAJOR progression in liver in only 6 weeks.
Dec 2010 - present - Ixempra/Avastin/Herceptin/Fasoldex - regressing
June 2012 - chemo break
Sept 19, 2012 - start t-dm1. Chose this over going back on Ixempra.
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Old 05-14-2011, 12:13 AM   #9
pibikay
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Great News
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Herceptin started again on 27th Dec 2012.Xeloda stopped Navelbin added on 7th February 2013.Now on Tykerb Herceptin and Navelbin
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Old 05-14-2011, 04:02 AM   #10
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Excellent news! News things on the horizon makes me confident that we WILL prevail!
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Diagnosed: June 2010, liver mets. ER-/PR+10%; HER2+++.
July 2010: Begin Taxol/Herceptin. Eliminate sugar from diet. No surgery or radiation.
January 2011: NED
April 2011: Progression in liver only. Other previous affected areas eradicated. Stop Taxol/Herceptin after 32 infusions.
May 2011: Brain MRI: clear.
May 2011: Begin Tykerb daily, Xeloda twice per day for one week on, one week off, and Herceptin.
November 2011: Progression in liver. All other tumors remain eradicated.
December 2011: BEGIN TRIAL #09-093 Taxol, MCC-DM1 (T-DM1), Perjeta.
Trial requires scans every six weeks, bloodwork and infusions weekly.
Brain MRI: clear.
January 2012: NED. Liver mets, good riddance!
March 2012: NED. Developed SMA (rare blood clot) in intestinal artery and loss of sight in right eye due to optical nerve neuropathy. Resolved when Taxol removed this month.
Continue Protocol of T-DM1 weekly and Perjeta every 3 weeks.
May 2012: NED.
June 2012: Brain MRI: clear.
June-December 2012: NED.
December 2012: TRIAL CONCLUDED; ENTER TRIAL EXTENSION #09-037. CT, Brain MRI, bone scan: clear. NED.
January-March 2013: NED.
June 2013: Brain MRI: clear. CEA upticking; CT shows new met on liver.
July 3, 2013: DISASTER STRIKES during liver ablation: sloppy surgeon cuts intercostal artery and I bleed out, lose 3.5 liters of blood, have major hemothorax, and collapsed lung requiring emergency resuscitative thoracotomy, lung surgery, rib rearrangement and cutting deep connective tissue, transfusion. Ablation incomplete. This life-saving procedure would end up causing me unforgiving pain with every movement I make, permanently, otherwise known as forever.
July 26, 2013: Try Navelbine/Herceptin. Body too weak after surgery and transfusion. Fever. CEA: Normal.
August 16, 2016: second dose Navelbine/Herceptin; CEA: Normal. Will skip doses. Watching and waiting.
September 2013: NED, Herceptin only. CEA: Normal. Started Arimidex.
October-November 2013: NED. Herceptin and Arimidex. CEA, CA125, 15-3: Normal.
December 2013: Something brewing. PET lights up on little spot on liver; CEA upward trend, just outside normal. PET and triphasic liver scan confirm Little Met. Restart Perjeta with Herceptin, stay on Arimidex. Genomic sequencing completed for future treatments, if necessary.
January 2014: Ablate Little Met on the 6th. Happy New Year.
March 2014: Brain MRI: clear. PET/CT reveal liver mets return; new lung mets. This is not funny.
March 2014: BEGIN TRIAL #10-005 A(11)-Temsirolimus plus Neratinib.
April 2014: Genomic testing indicated they could work, they did not. Very strange drug combo for me, felt weird.
April 2014: Started Navelbine and Herceptin. Needed something tried and true, but had significant progression.
June 2014: Doxil and Herceptin.
July 2014: Progression. Got nothing out of it. Brain: NED.
July 2014: Add integrative medical hematologist-oncologist to my team. Begin supplements. These are tumor-busting, immune system boosters. Add glutathione, lysine and taurine IV infusions every three weeks.
July 2014: Begin Gemzar, Herceptin & Perjeta. Happy.
August 2014: ECHO perfect.
January 2015: Begin weekly Vitamin D Analog infusions. 25 mcg. via port.
February 2015: CT: stable.
April 2015: Gem working, but not 100%. Looking into immunotherapy. Finally, treatments for the 21st century!
April 2015: Penn Medicine. Dendritic cell immunotherapy.
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Old 05-14-2011, 11:57 AM   #11
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

Ok, the advantages are that there is no risk to women with mouse allergies and this also spares the hamsters. What other advantages are there. I'm not good on science.
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Old 05-15-2011, 08:26 AM   #12
Lani
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Re: exciting new anti-her2 immunotherapy(fully-humanized,no Chinese hamster ovary nee

It fights the her2+ breast cancer in four different ways and is much more potent

I have a strong belief that if you weren't so afraid of trying to understand the sentences above, assuming only rocket-scientists could do so, and broke up the sentences and tried to understand a bit at a time (as if you were trying to read a foreign language) you could have figured that part out.


Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the [I]inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb.

Just like with a foreign language, you could see that the new compound has one more attribute than the three of what had been found before and that it is more potent.

You can also see that it describes herceptin as having cardiotoxicity and a substantial number of patients for whom it is not effective or becomes ineffective. That contrasts with the new construct which is selective for the cancer cells(avoiding the heart cells) and (the construct) has more mechanisms by which it works it seems.

Again, to read sentences, separate the words known from those not known (just like reading a foreign language). If some words look long and scary, substitute the words "chocolate" and/or "pecans" and or "whipped cream" them look up a few words if necessary and try to figure out what it is saying that way ie, as if it were French or Spanish or Italian.

If you add the culinary touches above, trying to read the "dry" material can be much more interesting!
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