Reprogramming the cancer microenvironment with vaccine-based therapy

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Published: 4 Apr 2016
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Prof Lei Zheng - John Hopkins Institute Baltimore, USA

Prof Lei Zheng speaks with ecancer and his research into vaccine therapies to treat pancreatic cancer.

Pancreatic cancer is notoriously resistant to many treatments, including checkpoint inhibitors.

Prof Zheng reports that using combined vaccine alongside anti-PD1 therapies primes the tumour microenvironment, increasing sensitivity and drug uptake.

 

3rd Immunotherapy of Cancer Conference (ITOC3)

Reprogramming the cancer microenvironment with vaccine-based therapy

Prof Lei Zheng - John Hopkins Institute Baltimore, USA


Pancreatic cancer is one of our focus because this is a disease with a very poor prognosis and in our study we find pancreatic cancer, even in the area of immune checkpoint inhibitors, still do not respond to the immune checkpoint inhibitor treatment. But we found with our vaccine treatment we can prime the tumour microenvironment and make it more sensitive to the immune checkpoint inhibitor treatment. We’re currently doing clinical trials to validate this concept and we have a clinical trial testing the combination of the vaccine therapy and anti-PD1 antibody therapy across all stages of the pancreatic cancer through four clinical trials.

What does priming the microenvironment entail?

We find in treated pancreatic cancer do not express the PD-L1 and also lack the effector cells infiltration. After the vaccine treatment we see the formation of the intratumoural essentially in every patient. We also see the upregulation of the PD-L1 signal in this. We tested the concept, the combination of the anti-PD1 vaccine in animal models and we see the synergistic effect between the antibody against the target PD1 and the vaccine therapy. That’s how we think the vaccine may prime the tumour microenvironment.

What have the trials shown so far?

We have one ongoing clinical trial to test the combination of vaccine and nivolumab, an anti-PD1 antibody. That study is still ongoing and today I showed one of my patients; she responded through the combination therapy, however it took about 4-6 months before she had a response. We also had a published study combining with another immune checkpoint inhibitor, ipilimumab, with the vaccine and we found three patients had a radiographic objective response and another four patients had tumour marker response. So one of the patients actually has had a long term disease free survival, had already been 5½ years out of the recurrent metastatic disease and still disease free after stopping the treatment for four years.

Could you tell us about what developments are on the horizon?

Yes, I just mentioned although we haven’t really finished the trials with vaccine in combination with nivolumab but, as I mentioned, the cases of my patients actually take about 4-6 months to have the response. Apparently this is a very aggressive disease, many patients were unfortunately taken off the study just after a month or two months of treatment due to the disease progression. So I believe the next step identify a target that can further enhance the anti-tumour therapy and also make these patients respond to the treatment quicker so more patients, I believe, will benefit from the immunotherapy.