2 oktober 2017: Bron: Algemeen Dagblad

Wanneer bij mensen een beginnend melanoom wordt gevonden en deze kan worden weggehaald en daarna op de plaats van de operatie wordt een injectie gegeven met een zogeheten DNA mengsel (CpG-B) dat lijkt op een lichaamsvreemde bacteriënmix dan wordt veel vaker een recidief voorkomen dan als alleen een operatie wordt uitgevoerd plus een injectie met een zoutmengsel (placebogroep). De DNA injectie geeft een enorme boost aan het immuunsysteem dat doordoor voorkomt dat er een recidief ontstaat of verdere uitzaaiingen.

Bij tot nu toe 52 behandelde patienten, die ruim tien jaar geleden met een verdachte moedervlek naar de huisarts gingen werd een melanoom in een vroeg stadium ontdekt.
Dertig patiënten kregen de stof CpG-B ingespoten. Twee van hen kregen jaren later alsnog uitzaaiingen en overleden aan de ziekte (7 procent). Bij de patiënten uit de controlegroep die geen injectie kregen ontstond een recidief en zaaide de kanker bij 40 procent van de patiënten alsnog uit. Zes mensen overleden; drie werden opnieuw geopereerd. Dit meldt het Algemeen Dagblad d.d. 2 oktober 2017.

Immuuntherapie met CpG-B wordt wereldwijd al heel lang onderzocht. Zoek in pubmed op CpG-B en je krijgt een aantal hits. De studie die nu wordt aangehaald van onderzoeker en medisch bioloog Tanja de Gruijl begon al in 2003 en werd gesloten voor patienten in 2007. En is in 2015 al gepresenteerd op het CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference

The researchers found that after a median follow-up of 76.5 months, two of the 30 patients assigned CpG-B and nine of the 22 patients assigned placebo had experienced melanoma recurrence.

Hier een beeld van twee patienten met elkaar vergeleken: (tekst gaat verder onder grafiek)

Fig. 4

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MAA-specific CD8+ T cells in the SLN. a MAA-specific tetramer+CD8+ T cell rates in the SLN of HLA-A2+ saline-administered patients are shown for tumor-negative and tumor-positive SLNs. Each dot represents one melanoma-specific tetramer-binding CD8+ population. The cutoff threshold set for positive tetramer responses is shown as a dashed line. b MAA-specific tetramer+CD8+ T cell rates in tumor-negative SLNs for all three groups. Below both graphs response numbers relative to evaluated numbers of patients and epitopes are shown. *p < 0.05

En toen al zei Tanja de Gruijl:

"Our results imply that local conditioning of the melanoma excision site by simple intradermal administration of an immune-stimulatory compound like CpG-B can lead to boosting of a systemic antimelanoma immune response that affords protection against recurrences in the long term, with minimal transient side effects," said de Gruijl. "We plan to conduct a large, randomized phase III clinical trial of intradermal CpG-B versus saline to confirm our findings of prolonged long-term recurrence-free survival."

According to de Gruijl, the major limitations of the study are that the data are the combined results of two phase II clinical trials with low numbers of enrolled patients and that different CpG-B doses were used in the two clinical trials. The low patient numbers mean that a large, randomized phase III clinical trial is needed to confirm the current promising findings, she added.

Nu twee jaar later worden alsnog in Nederland  de resultaten naar buiten gebracht. Met in het AD een herhaalde opmerking van Tanja de Gruijl uit 2015 maar nu in een Nederlandse krant: 

,,De verschillen zijn nogal overweldigend. Het lijkt erop dat een simpel spuitje veel ellende kan voorkomen. Maar let op: voor het op de markt komt, zullen we een vervolgstudie met een groter aantal patiënten moeten doen", zegt onderzoeker en medisch bioloog Tanja de Gruijl.

Waarom wordt dit nu pas allemaal naar buiten gebracht? En waarom moet dit nog eens tien jaar duren? Hebben ze geld nodig in het VUmc? Of is dit onderdeel van het lobbywerk om de EMA naar Amsterdam te krijgen? 

Voor het oorspronkelijke studierapport verwijs ik naar de twee fase II studies: Arming the Melanoma Sentinel Lymph Node through Local Administration of CpG-B and GM-CSF: Recruitment and Activation of BDCA3/CD141+ Dendritic Cells and Enhanced Cross-Presentation

en deze studie: Local delivery of CpG-B and GM-CSF induces concerted activation of effector and regulatory T cells in the human melanoma sentinel lymph node

Hieronder de referentielijsten behorend bij deze studies:

referentielijst behorend bij Local delivery of CpG-B and GM-CSF induces concerted activation of effector and regulatory T cells in the human melanoma sentinel lymph node

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referentielijst behorend bij Arming the Melanoma Sentinel Lymph Node through Local Administration of CpG-B and GM-CSF: Recruitment and Activation of BDCA3/CD141+ Dendritic Cells and Enhanced Cross-Presentation

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