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Immunotherapy development currently tends to focus broadly on three treatment categories: chimeric antigen receptor (Car) T-cell therapies, vaccines, and checkpoint blockade strategies. Car therapies, which coat the patient’s T cells to help those cells recognize tumor antigens, remain largely untested against breast cancer, so Mittendorf focused on vaccines and checkpoint inhibitors.

bei CART Technologie soll MGNX stark sein

Vaccine Leads Field

For patients with breast cancer, the most advanced vaccine is nelipepimut-S (neuvax). The formulation is a peptide derived from HER2 protein, combined with the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients receive it monthly for 6 months and then every 6 months thereafter for up to 3 years.

In a phase I/II trial as adjuvant therapy on 187 women with node-positive and high-risk node-negative tumors that expressed any degree of HER2, the 5-year rate of disease-free survival (DFS) was 89.7% overall for those who received the vaccine compared with 80.2% for unvaccinated women.1 For optimally dosed patients, the DFS rate rose to 94.6%.

The phase III PRESENT trial now under way seeks to randomize 700 women with early-stage, node-positive breast cancer with low to intermediate HER2 expression (HER2 1+ by IHC or HER2 2+ by IHC/FISH) to NeuVax or an active comparator composed of the GM-CSF sargramostim (Leukine).2 To be eligible for the trial, patients must have primary tumor stage T1-3 at initial diagnosis that was completely excised through surgery or are receiving neoadjuvant therapy before surgery.

mit Spannung erwartet

“Vaccination takes months to produce an immune response, so it’s probably not an appropriate treatment strategy for very late-stage cancers, but it appears to be particularly appropriate in an adjuvant setting,” said Mittendorf, who has been leading the nelipepimut-S trials.

Impfungen sind im akuten Stadium weniger wirksam, frühzeitige Behandlung wichtig (ähnlich Grippe Impfung)

“At that point, when most patients are already disease-free, harsh treatments make no sense. The tradeoff between toxicity and benefit is not in the patient’s favor. Effective vaccines, on the other hand, make perfect sense because they rarely subject patients to anything worse than mild pain or itching at the injection site. NeuVax is no more grueling than a flu shot.”

Nebewirkungen wie ne Grippeimpfung:)


There is also reason to think that many vaccines will prove more effective in the adjuvant setting than they have, to date, in the advanced-disease setting. Vaccines against infectious diseases rank among the most beneficial tools created by medical science, but they have a major limitation. They’re far better at prevention than treatment. In general, the more a patient already suffers from the target disease at the time of vaccination, the less a vaccine helps the patient.


“We don’t know enough yet to make blanket statements about the optimal timing for different immunotherapies, but anecdotal evidence suggests that vaccines are less effective in patients with advanced metastatic cancer,” Mittendorf said. “It would explain why many of the earliest vaccine trials, which enrolled patients with diffusely metastatic tumors, failed to demonstrate benefit.

Timing, in general, is critical in oncology, and it may prove particularly important with immunotherapy,” she said. “Research needs to demonstrate not only whether treatments work but when and how they work the best so that clinicians can prescribe each patient the right treatment at the right time.” - See more at: http://www.onclive.com/web-exclusives/Hope-Rises-for-Immunot…

Timing ist sehr wichtig

Gruss S.
 
aus der Diskussion: Sellas Life Sciences Group (ehemals Galena Biopharma)
Autor (Datum des Eintrages): Schaeffi  (31.03.15 08:40:35)
Beitrag: 874 von 2,935 (ID:49460948)
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