Generation of BiKEs and TriKEs to Improve NK Cell-Mediated Targeting of Tumor Cells

Tanuja Koppal:
Hello, I'm Tunja Koppal and I'm organizing a few different events at the Cambridge Healthtech Institute's upcoming World Preclinical Congress that takes place June 12th through the 16th in Boston. I'm delighted that Dr. James Hickman, who is one of our speakers, could take the time to join me today for this special podcast. Dr. Hickman is a founding director of the Nanoscience Technology Center and a professor of nanoscience technology, chemistry, biomolecule science, material science, and electrical engineering at University of Central Florida. Dr. Hickman, you will be chairing a session on exploring relevant in vitro models in the symposium on new tools for disease modeling on June 12th, and there you'll be talking about some of your work developing a human model of neuro-muscular junction activity for ALS and other neurological diseases, which sounds both exciting and challenging. Can you tell you us a little bit about the challenges with some of the in vitro models that are being used today, and how some of this work that you're doing right now can impact drug discovery going forward?

James Hickman:
As a lot of people know, the human-on-a-chip field is really taking off, because the field of drug discovery and also toxicology really is trying to minimize costs, trying to decrease the amount of time, and also the EU has banned the use of animals in testing cosmetics. So, that has become a key area for NIH to focus on, in funding. DARPA's also put a lot of money into funding that, but now pharmaceutical companies and cosmetic companies are also starting to look at these systems to be utilized in their processes.

So, one of the key aspects will be regulatory, in terms of trying to convince the FDA and the EMA to get approval of these new human-on-a-chip systems for use in either in [IND's 00:01:51], or giving them information for use in clinical trials.

So, one of the ways that's being addressed is actually we're running a workshop with AIMBE, which is the American Institute for Medical and Biological Engineering, in addition to NIH and the FDA, to look at the regulatory aspects. We've already run five of these workshops. So it's one of the biggest questions that people have is, "How are you actually going to get the FDA and EMA to utilize these systems, or approve the utilizations?"

Well, the five workshops have already been very successful. They have brought in people from the FDA and EMA to make very good suggestions on how to do these for efficacy, and also for toxicology purposes. And the sixth workshop will be held May 25th and 26th at [IHS 00:02:32] campus, and it will be focusing on, how you focus these systems on rare diseases? So, that will be this month, in a couple weeks.

Tanuja Koppal:
Also, you are giving a second talk at the conference on predicting direct toxicity. So it looks like these human-on-a-chip systems that you're developing have pretty diverse applications, all through the drug development process. So, can you talk a little bit more about some of the opportunities that these models present, and also some of their limitations?

James Hickman:
Sure. The systems that we're developing, Mike Shuler and I, are basically multi-chip systems are recirculating media. And they're in a serum-free media, so it makes them ideal for being able to evaluate not only drug candidates, but since we have liver present, also to look at their metabolites. And in our systems, what this allows us to do is look at efficacy and toxicology in exactly the same system. So now one can start looking at this as a very powerful tool, pre-clinical, for giving information not only on toxicity but efficacy, pre-clinical, but even pre-animal, using human cells.

It also allows us, because we're using non-invasive readouts, to be able to start looking at chronic. So if you really want to try to reproduce animals' data in these in vitro human systems, obviously long-term repeat of those experiments will be necessary, and our systems are uniquely capable of being able to do that.

And also how they're actually being constructed is, they can also be low-cost-based systems, because were using a pump-less based system that eliminate pumps and valves and bubbles, it makes them very straightforward to produce and to run the systems.

Tanuja Koppal:
So this workshop that you're organizing in collaboration with the NIH on May 25th and 26th, you mentioned that that workshop would focus on rare diseases. So, what are you hoping will be some of the key learnings from that workshop, that attendees working to join will know more about it?

James Hickman:
The workshop will be focusing on rare diseases, because that is one of the key areas of human-on-a-chip systems we believe will be able to address from ar regulatory standpoint, because rare diseases don't have a lot of patients. You can't think about doing large clinical trials. But yet you really want to try to have a safety and be able to know that there's some efficacy before you actually go into a patient. So by using a human-on-a-chip system, you can actually get a lot of this data, and then the FDA and EMA is very open to utilizing these systems, before being able to justify using for a rare disease certain drugs or treatments.

And so my talk during the upcoming conference in Boston, which is focusing on ALS, which is not exactly a rare disease, but it certainly doesn't have a huge patient population, and what we're doing is creating functional systems in neuromuscular junction, to be able to look and see not only what a disease neuron will do, but if we actually take these disease neurons and synapse them onto muscle, in a system where we can actually treat on the neuron side, or on the muscle side, this makes an ideal platform to be able to look at a very intractable type disease in a human-on-a-chip-based system, using induced [inaudible 00:05:31] stem cell derived motor neurons from ALS patients.

And so that's where we believe the regulatory aspects that this workshop will address will be able to take those exact same systems and show how they can be used for all kind of different rare diseases and start the conversation now, about how the regulatory folks would think about their utilization and what key questions they would have to ask, to be able to approve their use in allowing drugs to go forward into patients.

Tanuja Koppal:
And will the proceedings of this workshop be available to people who were not able to attend?

James Hickman:
I'm hoping to give a synopsis of the workshop's results at my talk in the [AHA inaudible 00:06:10] conference in Boston. And yes, we do publish reports form the workshops, and those will be available probably three to six months after the workshop.

Tanuja Koppal:
Thank you, Doctor Hickman, it was pleasure speaking with you today. Thank you for your time, and we definitely look forward to the workshop and also your presentations at the upcoming World Preclinical Conference in Boston.

For those of you who are listening to us, thank you for joining, and look forward to seeing you either at the workshop, or at the conference in June. More details can be found at worldpreclinicalcongress.com. And, Doctor Hickman, what is the website for your workshop?

James Hickman:
One could either go to the NIH NIBIB web page and find the link to the workshop, or you can also go to the AIMBE website, and it should be listed there. Or, if they're interested, they could always just directly email me.

Tanuja Koppal:
All right. Thank you once again, and goodbye everyone.