Article
Spanning two main islands, New Zealand is a unique country in the
landscape of immunology research. The country’s vibrant research
ecosystem fosters collaborative networks that extend from national
medical research institutes, including the Malaghan Institute of Medical
Research in Te Ika-a-Māui / North Island to world-renowned universities
such as University of Otago in Te Waipounamu / South island. In this
article we engage in conversation with Associate Professor Joanna Kirman
and Dr Rob Weinkove, about their dynamic collaborations with diverse
countries including Asia, Australia and the west-coast of America,
discuss New Zealand’s strong focus on translational research and
discovery, and consider the inclusion of Māori culture and perspectives,
into the experimental design, application and health outcomes of
scientific research in Aotearoa11Aotearoa loosely
translates from Māori as the “land of the long white cloud.” It has
been used by Māori to refer to the country for decades, if not
centuries.. Associate Professor Joanna Kirman (Figure 1) is a
distinguished immunologist and Associate Professor at the University of
Otago, whose work has made fundamental discoveries in understanding the
generation and maintenance of immunological memory in tuberculosis in
order to improve global vaccination strategies. Joining Kirman in our
conversation is Dr Robert Weinkove (Figure 2), an esteemed clinical
haematologist and Clinical Director at the Malaghan Institute of Medical
Research, investigating novel cancer immunotherapies with a focus on the
potential of CAR-T cells in blood cancers.
JB: I’m excited to have both of you speak about Immunology in
New Zealand, drawing on your diverse backgrounds and your geographical
divide. To start, I’d be very interested to know what got each of you
excited about immunology. What led you to where you are now?
RW: I’m a clinician by training, having trained in haematology
in the UK and Germany. In haematology, we spend much of our time
treating immune system cancers, in fact, we mainly treat cancers of
antigen presenting cells (cancers of B cells and myeloid cells). We
often treat with various forms of immunotherapy, including allogeneic
bone marrow transplantation, which itself can be regarded as an immune
system transplant. We do it all by recipe, essentially, empirically
following specific protocols - giving a bit more cyclosporin or steroids
if patients get graft-versus-host disease and giving a less if they
don’t. In London, I would see patients for whom these transplants would
go very well, and others for whom they would go very badly. And while
the chances of success are often weighted one way or another, it feels a
bit like a roll of the dice each time I refer someone for an allogeneic
bone marrow transplant. What became fascinating for me, was the chance
to use much more targeted immunotherapies, with more defined risks and
benefits. The field of human cancer immunotherapy has taken off,
particularly during the last five years with the uptake of CAR-T cell
therapies and bispecific T cells, so for me it’s an exciting time to
work at the interface of immunology and haematology.
JK: My excitement about immunology started while I was doing
undergraduate biochemistry and I took an immunology paper in my last
year. I just loved it. I went on to do a summer project, where I then
proceeded to switch departments and undertook an honours project in
Immunology. I thought, “this is what I want to do” and I’ve stayed in
immunology ever since. I can’t put my finger on what it was about
immunology that captured me, perhaps the complexity of the network and
how it all fits together. Its intriguing how it all kind of makes sense
and then it sort of doesn’t. It really got my imagination going and has
ever since.
JB: Throughout your immunology journey, what do you think has
been your most significant discovery or contribution to immunology? It
doesn’t have to be Nobel prize winning, it can be tiny, but what do you
look back on and think of how proud or excited you are about that part
of your immunology research to date.
JK: For me it has been recognising very early on that TH1 T
cells were not the Holy Grail that people had thought they were in terms
of vaccines for tuberculosis (TB). Coming to that realisation and very
early on when most people were still chasing after T cells is one really
significant part of my research. We published a commentary review early
on summarising some of the perspectives on DNA vaccines and the role of
protective memory T cells, and after I recently presented a careers talk
for the New Zealand branch of the ASI, I realised even in my PhD I was
writing about these perspectives. It’s just taken a very long time for
some of the TB community to think outside of the conventional box in
terms of looking beyond adaptive immunological memory and considering
that there are other cells that are doing things that are pretty
important with regard to immunological memory.
RW: For me, the first immunology work that I did was my PhD
with Professor Franca Ronchese and Professor Ian Hermans at the Malaghan
Institute. I’d generated the topic myself based on what my supervisors
were doing and my interests in haematology. I was interested in the
immune system dysfunction that you see in patients with blood cancers,
including chronic lymphocytic leukaemia (CLL), and studied natural
killer T (NKT) cells in this condition. I have to say, the experimental
work was horrible! Human NKT cells are rare at the best of times, and
when you’ve got a patient for whom 99% of the circulating cells are
leukemic cells that you have to deplete before you can do anything else,
it’s really hard to do functional assays. I’ve remained interested in
this field, because what’s happening with blood cancers is that we’re
getting better and better at treatment, and at keeping more patients
alive for much longer, but infection is a growing risk. In fact, it’s
getting to the point with CLL and some other blood disorders that we
will soon see more people dying of infection than of the malignancy
itself. It’s been great to have been able to take part in design of a
new international platform trial examining antibiotic prophylaxis and
immunoglobulin replacement in patients with CLL and related conditions
through the Australasian Leukaemia Lymphoma Group and with Monash
University. We’ve described the immune dysfunction, and can now
contribute to overcoming it through to what hopefully will be a
practice-defining study. What’s most exciting to me at the moment in my
own lab is our work on an unusual CAR-T cell construct, which uses part
of Toll-like receptor 2 as a costimulatory domain – we have completed a
dose escalation phase 1 clinical trial with this new CAR T-cell
construct, and are now in dose expansion (clinicaltrials.gov
NCT04049513).
JB: You’ve both made some landmark discoveries, but in such
different fields. I would now like to talk about something you just
touched upon Rob, in regard to your collaborations with Canada and also
Monash University in Australia. As you both do very different types of
research, how do you each find the research landscape of where you are
situated in respect to collaborations in your institutes/Universities,
across New Zealand and internationally?
RW: I’d say New Zealand’s a bit like Australia in that the
journeys between major cities are quite long by road, so we tend to fly
between cities. I don’t feel any more distant from Dunedin or
Christchurch than I do from Auckland, even though Auckland is on the
same island as Wellington, so I wouldn’t say the Cook Strait itself is a
big barrier. There is always a degree of siloing within and between
institutions purely because you are most familiar with the people work
with every day. One comment I’d like to make is that I always thought I
would retain strong European collaborations having worked in the UK and
Germany, but time zones make a real difference. Recently, we’ve had more
productive collaborations with Australia, China and the West Coast of
the US, I’m thinking in part because the time differences are
friendlier.
JK: I completely agree. My main collaborators are based in the
US, one of my postdocs from my lab just spent 6 months working with a
group over there, but the collaborators do tend to be more on the West
Coast. The time difference is hard when you’re trying to have meetings
and maintain collaborations. As Rob said, particularly in Dunedin in the
South Island, we have fewer flights coming in and out than in Wellington
or in Auckland which are both in the North Island, so it is actually
quite a mission to get to another city. Our ability to travel was also
stunted over the past couple of years due to the pandemic.
JB: Rob you are in a medical research institute and Jo you are
at a University, both in very different geographical locations. What are
the research focuses like where you are? Is there quite unique research
or technologies where you are?
JK: It’s not too different in terms of the research coverage.
In both places there are cancer researchers and infectious diseases
researchers. We probably don’t have anyone, and I don’t know whether the
Malaghan has anyone who’s just doing pure immunology without an applied
nature to it.
RW: The Malaghan Institute is quite focussed on translational
immunology – in recent years we have run clinical trials of dendritic
cell vaccines, CAR T-cells, experimental hookworm infection, and
observational vaccine studies. We do have some pure immunology too; for
example, Professor Franca Ronchese has a programme investigating
dendritic cell (DC) biology.
JB: Would you say that most immunologists in New Zealand are
doing quite translation focused research? Does this mean most
researchers have good clinical or hospital connections?
RW: Our main granting bodies see a pathway to translation as a
required or very important feature of funded research. That does
influence what people do. One important point to make its that the
health system here is stretched, as it is around much of the world at
present. So, while there’s often a desire from scientists to collaborate
with hospitals, the capacity of the hospitals to assist needs to be
considered. Navigating that interaction is much of my day-to-day life –
it’s interesting to come up with creative solutions for getting
translational work done. We’re fortunate to have a Good Manufacturing
Practices (GMP) facility with a licence for manufacturing lentiviral
vectors and CAR-T cells, which means we can run early phase CAR-T cell
in-house. This emerged as a result earlier dendritic vaccine trials,
first started by Dave Ritchie, now in Melbourne, with Ian Hermans. We’re
seeing more and more applications of Immunology: new immunotherapies for
cancers and non-malignant disorders, monoclonal antibodies for
everything, and RNA vaccines. It’s hard to find much immunology that
hasn’t got some potential link into the clinic.
JB: Just highlighting your comment about the GMP facility. Is
that also for commercial purposes? Do you see much commercial
translation going on in New Zealand?
RW : Our funders are keen that we seek commercialization
opportunities. For our own CAR-T cell programme, we’ve set up a couple
of start-up companies as a way to bring in commercial funds. We don’t
have a Medical Research Futures Fund (MRFF) or equivalent here in New
Zealand, so it is important to identify other sources of funding.
JK: I suppose we have different strengths and linkages. For
example, my lab (Figure 3) is looking at a disease, TB, that’s not
particularly common in the South Island. We do have the Centre for
International Health at the University of Otago, down in Dunedin and
they have clinical collaborations in locations where TB is endemic. For
example, one of my collaborators has linkages to Indonesia, where they
have established clinical studies looking at Bacille Calmette-Guérin
(BCG) vaccination and transmission in highly exposed individuals, which
is something that we just can’t do in New Zealand so there is a
potential then to set up more trials. In Dunedin, we’ve got a very high
incidence of colorectal cancer, probably higher than anywhere else in
New Zealand, so there’s a quite a few groups looking at colorectal
cancer and the immunology behind it. There are also other labs
developing linkages with the Pacific, to research the diseases that are
affecting people in Pacific nations in order to find ways of supporting
them, so we do go beyond our little city.
JB: You’ve both touched upon different forms of funding, so I’m
interested to understand what the funding landscape is like in New
Zealand?
JK: It is tight, which is something I don’t think anyone would
disagree with. We’ve got our staple grants including Health Research
Council (HRC) and Marsden, and also have some larger of pots of money
that are very focused. These strategic funding opportunities include the
RNA Development Platform and Te Niwha, the Infectious Disease Research
Platform.
RW: There are Ministry of Business Innovation and Employment
(MBIE) funding streams, which we’ve made use of, that have strong
commercialization angle. I’m not sure that any of the funding
opportunities in NZ are all that different to anywhere else. One thing
to note is that the size of most HRC grants hasn’t gone up for many
years, which makes it hard to cover salaries.
JB: Along the lines of funding and research opportunities in
New Zealand, what are the opportunities for PhD students and early
career researchers (ECRs) coming to New Zealand? Are there competitive
fellowships or other financial supports they can apply for?
JK: International students are eligible for university PhD
scholarships. They generally have to be very high achieving students to
be successful. All of our grants, for example, can have a PhD student
written into them and it would fund any PhD student who applies. There
are also some of the centres of research excellence which offer
opportunities for potential students to apply for funding.
RW: It’s not infrequent that we recruit postdocs from overseas,
usually as a later stage ECR, as we are looking for people with unique
skill sets to add to our research expertise and grow our lab. We also
encourage people who’ve done a PhD with us to go and gain experience at
overseas labs and grow the group’s international reputation. We also
hope to get those people back to NZ later on, to run our labs in the
future.
JB: What has impressed me over the years, especially with the
more kiwi’s22Kiwi is a slang term for a person from New Zealand.
I’ve met regardless of their profession, is their understanding,
inclusivity and genuine connection to Maori culture. How do you
incorporate indigenous culture considerations into your research and in
the medical research landscape in Aotearoa?
JK: I think that all laboratories in New Zealand try to uphold
tikanga Māori / Māori customs and ideals. For example, in terms of not
storing certain things together that shouldn’t be together, researchers
would not store animal cells and human cells next to each other. There
are certain types of practises that we try to make sure we adhere to and
many of them are really interesting. For example, our PC-2 practises
align really beautifully with a lot of tikanga Māori. There’s an idea of
tapu and noa33Tapu is te reo Māori for sacred or restricted; noa
is te reo Māori for common or ordinary., such as it’s offensive to
sit on a table as the table is tapu whereas our bottoms are noa. Equally
so, in a PC-2 lab you would never sit on a lab bench. These practices
align quite beautifully with each other. Implementing tikanga Māori in
the laboratory is something that probably most laboratories would do
now, but we’re still on a learning curve as well. We might be a bit
further ahead than in Australia, but we’re still learning. One of the
big things that we’re really trying to do is build capacity within the
Māori and Pacific population so that we have research leaders who
identify as Māori or Pasifika as currently there are very few. We are
also working to make our labs a welcoming place for our Māori and
Pasifika students. This is the reason I am learning te reo Māori.
RW: The impact and the consideration of Māori health in the NZ
health sector is something that can’t be overstated. The Treaty of
Waitangi is regarded as the founding document of New Zealand, and has
been interpreted as requiring equity of health outcomes for
Māori, not just equality of healthcare access. There’s a clear and
immediate imperative to try and achieve that, which is a really big
task, because there are social and economic inequities as well. Equity
of health outcomes for Māori is a huge focus in the health service and
in the way the government is investing into health research. For
example, for our CAR-T cell trial, I have a monthly meeting with a Māori
haematologist and equity specialist. We look at enrolment rates, and we
have changed elements of our patient information sheets and our
inclusion criteria. As a result, we are seeing good representation of
Māori among CAR T-cell trial participants. Then there is the element of
tikanga, or cultural protocols, relating to cells and genetic code, as
Jo has said. When I first came to New Zealand in 2008, I perceived a
reluctance to conduct genetic research involving Māori. I think that
this view has changed, because it’s clear that to gain benefits of
health research, Māori participation is key. Importantly, this research
has to be conducted with Māori researchers helping to determine the
research questions, and as part of the research team. At the Malaghan
Institute, a Māori steering group, Te Urungi Māori, helps guide us. My
lab co-supervises a Māori PhD scholar undertaking a mixed-methods PhD,
part of which involves looking at tikanga relating to CAR-T cell
therapies. It will take time before we have a truly representative
senior research workforce, but I’d say these efforts are clearly
underway.
JB: The research landscape definitely sounds unique in New
Zealand, and I am sure enticing for many. I have great memories of New
Zealand, and I would like to hear, apart from the research, why should
people consider coming to New Zealand to work?
RW: The outdoors! New Zealand a fascinating country, and is
simply beautiful. You can drive from one side of an island to the other
in a day and see mountains or volcanoes, and two different coasts. You
can walk in the bush, go skiing or mountain biking, or go surfing.
Nature offers amazing activities for your downtime.
JK: I live in a much smaller city than Rob and, at the end of
the day, you can go and do some really cool things. Everything is just a
short drive away, even in Wellington. In Dunedin everything is 10
minutes away and in Wellington it’s probably 20. Everything is very
accessible.
JB: Thank you to both of you for providing so much insight into
the accessibility and inclusivity of New Zealand research and healthcare
outcomes.
_______