01 Oct Vaccinating New Melanoma Patients With Immune Booster Reduced Tumor Recurrences
MedicalResearch.com Interview with:
Tanja D de Gruijl PhD
Professor Translational Tumor Immunology
Head Immunotherapy Lab
Department of Medical Oncology
VU University medical center-Cancer Center Amsterdam
Amsterdam, The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. de Gruijl: Patients that have just been diagnosed with melanoma after heaving a suspect mole removed, at this moment in time don’t have any treatment options to eliminate any sub-clinical micrometastases that (sometimes years later) can grow into distant tumors. These patients, even at these early stages of melanoma, nevertheless run a risk of this happening (between 10 and 30%, depending on local tumor penetration and spread) and all they can do is wait and it see if the surgical removal of the tumor came in time. We reasoned that if we could boost immune cells directed against the tumor in the first-line melanoma-draining (i.e. sentinel) lymph node that remained after removal of the primary tumor we could achieve a systemic immune response against the tumor that would provide a body-wide protection against outgrowth of metastases at a later time. We indeed found (and described in publications) that we were able to boost anti-tumor immunity in this way, by locally injecting the immune stimulatory compound CpG-B into the scar at the site where the primary melanoma was surgically removed, in the week leading up to the surgical removal of the sentinel lymph node. CpG-B resembles bacterial DNA and alerts the immune system to a possibly dangerous infection, thus effectively inducing immune activation. We performed two randomized clinical trials and found T cells recognizing protein fragments associated with melanoma tumors to indeed be expanded and activated in the tumor-draining sentinel lymph node but, importantly, also in the blood of the treated patients. In patients who were administered a placebo control these effects were not observed. We are now seven to eleven years on from when we carried out these trials and have performed clinical follow-up on these patients. We are excited to conclude that patients treated with the CpG-B compound have indeed experienced fewer tumor recurrences during that time (only two out of 30) than patients from the control group who show the (expected) higher rate of tumor recurrences (nine out of 22).
Medical Research: What should clinicians and patients take away from your report?
Dr. de Gruijl: Our results seem to imply that local conditioning of the tumor excision site by simple intradermal administration of an immune-stimulatory compound like CpG-B, can lead to boosting of a systemic anti-tumor immune response to such an extent that it affords protection against recurrences in the long-term, and, importantly, with minimal and transient side effects. This would mean that for the first time there’s a real hope for an effective adjuvant therapy following surgical removal of an early-stage melanoma tumor. However, it is important to stress that these were the compiled data from two relatively small (albeit randomized) trials and that our findings need to be confirmed in a larger randomized follow-up trial.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. de Gruijl: First of all to plan a larger randomized Phase-III trial to hopefully confirm these data.
Second, to also study the effects of other novel immune stimulatory agents that may be similarly used to treat early-stage melanoma patients with the aim to prevent tumor recurrence.
Alone or combined these may prove a valuable but relatively cheap therapy option with wide applicability and potentially high impact.
Abstract presented at the
AACR: CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
Sept. 16–19 2015
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Tanja D de Gruijl PhD (2015). Vaccinating New Melanoma Patients With Immune Booster Reduced Tumor Recurrences