excellent results of small (7 patients) Duke her2 dendritic cell vaccine

[Lani]

J Transl Med. 2007 Sep 6;5(1):42 [Epub ahead of print] Links
Long Term Disease-Free Survival and T Cell and Antibody Responses in Women with High-Risk HER2+ Breast Cancer Following Vaccination Against HER2+

Morse MA, Hobeika A, Osada T, Niedzwiecki D, Marcom PK, Blackwell KL, Anders C, Devi GR, Lyerly HK, Clay TM.
ABSTRACT: BACKGROUND: The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses. METHODS: Subjects with stage II (_ 6 +LN), III, or stage IV breast cancer with >50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n=3), mature cultured DC (n=3), or mature Flt3-ligand mobilized peripheral blood DC (n=1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact. RESULTS: All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6-6.7 years of follow-up. CONCLUSION: Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population. Trial Registration: ClinicalTrials.gov NCT00005956.
PMID: 17822557 [PubMed - as supplied by publisher]

[lexigirl]

That sounds so great!! Somebody sign me up!!

Thanks Lani,
Lexi

[lilyecuadorian]

I' m going to ask my doctor ..and see what he thinking ....thank Lani for good news ..

[TSund]

Lani, THX for this! Sounds promising and we will speak to onc about it as Ruth's surgery 10/11.

Doesn't sound like anyone in trial did pre-surgery chemo?

[Joanne S]

Summary
Expert Review of Vaccines
August 2007, Vol. 6, No. 4, Pages 617-633
(doi:10.1586/14760584.6.4.617)

<!-- End title of page and review --><!-- Start full text content -->

<!-- abstract content -->Dendritic cell vaccination
Owen Proudfoot, Dodie Pouniotis, Kuo-Ching Sheng, Bruce E Loveland and Geoffrey A Pietersz<SUP></IMG></SUP>† Author for correspondence



There has been a surge of interest in the use of dendritic cell (DC) vaccination as cellular immunotherapy for numerous cancers. Despite some encouraging results, this therapeutic modality is far from being considered as a therapy for cancer. This review will first discuss preclinical DC vaccination in murine models of cancer, with an emphasis on comparative studies investigating different methods of antigen priming. We will then comment on the various murine DC subsets and how these relate to human DC preparations used for clinical studies. Finally, the methodology used to generate human DCs and some recent clinical trials in several cancers are reviewed.

<!-- /abstract content --><!-- fulltext content --><!-- /fulltext content -->

[Lani]

and in generally articles are written and submitted long before they come out so can't be all inclusive. They, in addition, usually rely only on what has already been published (as verbal reports of studies in progress can only be referred to and qualified by something like "personal communication, unpublished")

Hope they expand the study soon.

[Joanne S]

DUKE CONCLUSION: Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population.

I agree with you, the review I posted was published before the findings of the Duke Study. Although the Duke Study produced excellent and VERY promising results (per above DUKE CONCLUSION), the responses to your post suggest that these ladies seem anxious for immediate inquiry to their physicians when it is so very far from being available---just wanted to clarify to avoid possible misunderstanding. I hope this helps to clarify.

I am neither a doctor nor nurse so usually I'm lucky if I understand half of what I read on trials, reviews, findings... so I'm not sure if the following is exactly the same as the dendritic cell vaccine; if you and anyone else interested in checking, there are studies for NEUVENGE for HER2 breast cancer---it is similar or possibly the same as PROVENGE for prostate cancer which came very, very close to being approved earlier this year by the FDA.

Best to you.

[TSund]

I had actually assumed this is probably still in the study phase. However, our onc is very much involved in the research part of things and would know and probably encourage any studies Ruth is eligible for.

If anyone gets further news, please post!

THX

TRS

[MJo]

I have recently read about Neuvenge, a Her2 vaccine by the makers of Provenge, a prostate cancer vaccine. I believe it's going into Phase 2 Clinical Trials. Anybody know more about this? THere was a flurry of news a few weeks ago. Even made the National Enquirer.

[Becky]

I think it was posted here somewhere, MJo.

The dendritic effect is why I took Leukine instead of Neulasta or Neupogen. Leukine boosts the dendrites as well as the other components of the white blood cell system.

[fullofbeans]

Thanks Lani again for bringing such quality studies to our attention.

Breathing hope into us each time you do, thank you.