Tuesday, May 9, 2017

Survival with dendritic cell vaccine about the same as survival produced with ipi

I have always, and still do, hold great hope for a vaccine that is REALLY effective for melanoma.  However, positive results have been few and far between.  My study was actually a combo of nivo and peptide vaccines.  In 2013, we ratties proved that those vaccines worked NOT AT ALL (and it is possible they even diminished our response by sequestering our t cells!!!):  Peptide vaccines do NOT trigger effective immune reponse to melanoma!!!! Of mice and men....

In 2015, there was this, on a different peptide vaccine:  Positive response to Helper Peptide Vaccines for melanoma

In 2016 there was a lot of talk about dendritic vaccines:  Dendritic cell vaccines. Perhaps this approach will allow vaccines to live up to their potential for melanoma....SOON!!!

Now there's this:

Twelve-year survival and immune correlates in dendritic cell-vaccinated melanoma patients. Gross, Erdmann, Haendle, et al. JCI Insight. 2017 Apr 20;2(8).

Reports on long-term (greater than/= to10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup.

Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides were injected intradermally in high doses over 2 years. We performed serial immunomonitoring in all 53 evaluable patients.

Vaccine-specific immune responses including high-affinity, IFNγ-producing CD4+ and lytic polyfunctional CD8+ T cells were de novo induced or boosted in most patients. Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not further enhance such immune responses, while keyhole limpet hemocyanin (KLH) pulsing to provide unspecific CD4+ help promoted CD8+ T cell responses - notably, their longevity. An unexpected 19% of nonresectable metastatic melanoma patients are still alive after 11 years, a survival rate similar to that observed in ipilimumab-treated patients and achieved without any major (more than grade 2) toxicity. Survival correlated significantly with the development of intense vaccine injection site reactions, and with blood eosinophilia after the first series of vaccinations, suggesting that prolonged survival was a consequence of DC vaccination.

Long-term survival in advanced melanoma patients undergoing DC vaccination is similar to ipilimumab-treated patients and occurs upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine injection site reactions occurring after the initial vaccinations.

And as far as those eosinophils???  Remember this?  Eosinophilia - biomarker for prognosis in melanoma and importance in immunotherapy response

With this level of response, dendritic vaccines certainly deliver something!  However, with a 40% response to anti-PD-1.....I would have a hard time picking ipi or these vaccines as my treatment if I had a choice.  Perhaps these vaccines WOULD be a good choice as adjuvant?  Perhaps as a combo with anti-PD-1?

Hang tough ratties.  We have a long way to go....but we've come a long way baby!!! - c

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