Combining the SLP vaccine with chemo-immunotherapy in order to increase the HPV-specific T-cell response in cervical cancer

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Published: 15 Apr 2019
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Prof Kees Melief - Leiden University Medical Center, Leiden, Netherlands

Prof Kees Melief speaks to ecancer at the 2019 American Association for Cancer Research (AACR) meeting about a study looking at the HPV-specific T-cell response after chemo-immunotherapy for advanced cervical cancer.

Prof Melief discusses the favourability of cancer vaccines due to the way they can be easily applied to large numbers of patients, their low cost and that when combined with chemotherapy and immunotherapy they can have great benefit.

He reports that the focus is on virus-induced cancers as the antigens are expressed in all cancer cells making them very good targets.

 

I’m in immuno-oncology and for years I’ve been interested in cancer vaccines because they are relatively easily applied to large numbers of patients. They can increase the general numbers of T-cells in patients at relatively low cost compared to cellular treatments. Then if you combine them with immunomodulators and chemotherapy you can incur tremendous benefits.

What are the main challenges that you have to overcome?

The main challenge is that we are a small biotech company but we have teamed up with a large pharma, Regenera, is to really rapidly arrive at a phase III registration trial that would allow the drug to become registered and become available to large numbers of patients.

What particular project are you focusing on currently?

Currently we are focussing on virus-induced cancers because the antigens of the cancer in the case of human papilloma virus are expressed in all cancer cells so they are very good targets. Also because the two oncogenic proteins, E6 and E7, are themselves involved in the malignant transformation so tumour cells cannot afford to lose these markers and so they are excellent targets for T-cell targeting.

Is this strategy being accepted or is it something there is resistance to?

Yes, people are definitely accepting this although there was a fair degree of scepticism about therapeutic cancer vaccines but slowly this is ebbing away because people are seeing the benefits of vaccines next to checkpoint blockers. We already published the combination of checkpoint blocker plus our vaccine actually doubles the overall response rate from 16% to more than 36%. Also the overall survival is doubled, more or less, in patients with HPV16 positive head and neck cancer.

Will this develop into further combinations?

Definitely because we have now separately shown that there is benefit from a combination of our therapeutic vaccine against HPV16 with chemotherapy on the one hand and with checkpoint blocker on the other hand. So now in patients with late stage cervical cancer we would like to combine all three modalities, so chemotherapy, checkpoint blocker and vaccine.

Is there anything else you would like to add?

We need to look at HPV16 induced disease as a global problem. Currently we have excellent screening in women in the developed world where the cytology screening has been replaced by HPV16 and other high risk type determinations which is more reliable even than cytology. But in the less developed world there is no screening at all and no HPV detection so in those countries HPV induced disease is a huge problem and that’s why by the time it is being detected as a cervical cancer, for example, in women it’s too late in most cases. So what we need to do there is to have measures like our type of immunotherapy to be able to help those patients as well.