Antibody-based and bispecific T-cell dependent therapies

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Published: 23 Sep 2016
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Dr Nai-Kong Cheung - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Cheung speaks with ecancertv at Childhood Cancer 2016 about his plenary session, focussing on antibody therapy for childhood leukaemia.

He describes how the engineered arms of a Bispecific T cell Engager (BiTE) can be used to deliver radiotherapy to tumours selectively.

BiTE therapy is also discussed by Dr Straathof here


Childhood Cancer 2016

Antibody-based and Bispecific T-cell dependent therapies

Dr Nai-Kong Cheung - Memorial Sloan Kettering Cancer Center, New York, USA

I actually gave a talk at the plenary session on immunotherapy and honestly this is an interesting and exciting meeting to hear about what’s going on, not just in immunotherapy but really on the genomics of cancer in children. I think it’s something that is of great importance because it is the kind of cancer that’s neglected, not because people don’t care but just it’s not getting the kind of awareness that it really should.

Can you tell us a little more about your work looking at bispecific antibodies?

We have been looking at antibodies for thirty years and we’ve done a lot of work with getting drugs to the patient. We make a lot of antibodies and I think that we really make a difference in terms of the long-term outcome. We are beginning to see our children now growing into adults, they’re getting married, they’re having children and I’m excited about it but not everyone is so lucky. There are still quite a few patients who never get cured and that’s really where we want to take the next leap forward and that is really looking at T-cells. These are cells that we haven’t been using in the past and these are the cells that are really powerful professional killer cells that we really want to take advantage of. This is how we build these bispecific antibodies and now can attach essential like handcuffs to T-cells to the tumour and let them fight it out. Of course you know who’s going to win, it’s the T-cells.

Could you tell us more about GD2 and CD3 in particular?

GD2 is a target that is really abundant on tumour cells and this has been the target we’ve been going after all these years. Now when I mentioned the handcuff, essentially the handcuff goes on one hand to the GD2 and the other hand is the CD3 which is on T-cells and then you get them together.

And this is being used to deliver radiotherapy?

That’s another thing, we are building another kind of bispecific antibody where one end is GD2, again hooking to the tumour, and the other end is actually bringing in a small little ligand called DOTA. What this thing does is it carries with it a radioisotope, it could be an alpha emitter like an atomic bomb or a beta emitter like what we use for thyroid cancers for example. So we now have this ability to bring isotopes, in fact a good use of isotopes, to treat patients, something that Madame Curie has dreamed many years ago, now we’re just beginning to actually be able to use it, not so much as external beam radiation but as a liquid radiation which I think must be a very interesting approach.

Is there a risk of doing damage?

That’s something particularly important in children because we’re not just keeping them alive for a few years, we want to keep them alive for the next hundred years. And if we cannot keep them alive and making every single organ function the normal way, it will be a problem so late toxicity has always been an issue. Any of the treatments that we give we always have to look at the long-term; whether this is T-cells or radioisotopes we need to be sure that the method that we use is not going to damage any of the vital organs. I think that we’re making a lot of progress - we are able to identify what are the risk factors certain patients may have, how can we cut back the innocent bystander damage. We’re getting much better now these days in reducing these late effects.

Is there anything else you would like to add?

I think that this is the era where I’m as excited as I was thirty years ago and I think I’m even more excited because of all the possibilities. There are now many still hurdles in trying to get drugs to the people, to the patients, to the children, but I think it will take some work and I think that if there’s a will there’s a way.