Comment: HPV-targeted adoptive T cell therapy may provide a new strategy for advanced cervical cancer

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Published: 2 Jun 2014
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Dr Steven O'Day - Beverly Hills Cancer Center, Los Angeles, USA

At ASCO 2014, Dr O'Day provides ecancertv with his expert opinion on the results of a phase II study which show significant results in several women with advanced cervical cancer, using a new type of personalised immunotherapy known as adoptive T cell therapy.

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ecancer's filming at ASCO has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

It’s a very labour intensive process. This has been worked out well with Dr Rosenberg’s scientific team at the National Cancer Institute over the last several decades in melanoma. But even though the science is improving how we do it, it still needs to be done at large academic centres and it’s very labour intensive. I think today, though, the message is whereas in melanoma we have all the checkpoint inhibitors and it’s transforming therapy, in other solid tumours we may have more challenges and this type of approach where you actually take the T-cells out of the tumour itself and grow them up, select them for the ones that are most immunogenic, in this case it was two viral proteins, HPV virus on the cervical cancer, grow them up and then re-infuse them with high doses of IL2 in a cancer that normally wouldn’t provoke much of an immune response. That’s the message, that we can take cancers that are hidden to the immune system and expose them, we’re bleeding them so that the T-cells can see better and attack.

From past experience, long ago we used to think of immunotherapy as being a relatively low key affair that is well worth doing and actually prevents some diseases altogether but in the case of cancer not a big issue. What’s happening here?

It’s just phenomenal that the state of immunology, the science of immunology, because before we spent a lot of time worrying about vaccines and stuff to try to prevent recurrences of small little tumour cells. Here with the science of understanding these checkpoints that are powerful, it’s worth taking people with widespread cancer and causing a rejection of the cancer through the immune system.

We heard about two cases, two patients who had complete regression of the disease; as far as they’re concerned they’re cured and it was extensive disease. Do you think they are cured for long?

If it holds up, if the melanoma data with these adoptive T-cells holds up, they have a very high chance of being cured.

And in cervical cancer with this one?

I think so; I think they have a very high chance. And these are young women who had failed multiple chemotherapy directed therapies and it just shows you that by not focussing on the cancer cell but letting the immune system do the work that historically that has led to durable responses.

There could be big patient pressure to get this sort of therapy but is it deliverable because of the labour-intensive nature?

Right now it’s being performed in cervical cancer at the National Cancer Institute. I think the concept in melanoma has been worked out with other centres, MD Anderson, Moffitt and others. Some of Dr Rosenberg’s colleagues have started to set up at multiple other areas in the US. I think as this expands into other diseases obviously more centres will be activated but it’s not treatment in the community, this is highly specialised care.

T-cell therapy is a very sexy subject but it might not be very widely available.

Adoptive T-cell. What I would argue is the checkpoint inhibitors, it’s T-cell therapy in vivo.

But the adopted T-cell...

I think we have a ways to go to make it exportable to large numbers. I think it will get there but I think we have a ways to go for that.

So what would you say to busy cancer doctors with patients with advanced cervical cancer?

Obviously each patient is different in their set of circumstances but certainly, based on this data with an open trial at the National Cancer Institute, they should be considered and talk to the investigators at the National Cancer Institute to see whether their patient might be appropriate for this approach.

So you do think this could be translatable into community care?

No, I don’t think it should be done in the community at this point, there’s no way it can be done in the community, but community doctors should consider referrals for this treatment to the National Cancer Institute and others.

So it could be used by ordinary patients?

Yes.

And become routine?

I think more patients may be applicable to this than we had anticipated.

But of course this is only nine patients so far, we can’t read much into it.

It is. It’s very early.