The Immune System and Melanoma

August 02, 2021

Information

August 1, 2021

Yale Cancer Center

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00:00Funding for Yale Cancer Answers
00:02is provided by Smilow Cancer
00:04Hospital and AstraZeneca.
00:08Welcome to Yale Cancer Answers
00:11with your host Dr. Anees Chagpar.
00:13Yale Cancer Answers features the latest
00:14information on cancer care by
00:16welcoming oncologists and specialists
00:18who are on the forefront of the
00:20battle to fight cancer. This week,
00:22it's a conversation about Melanoma
00:24with Doctor Harriet Kluger.
00:25Doctor Kluger is a professor of
00:27medicine and medical oncology
00:29at the Yale School of Medicine
00:31where Doctor Chagpar is a
00:33professor of surgical oncology.
00:37I thought that we would dive
00:40right into the treatment of Melanoma.
00:43We've talked a lot on this show
00:46about Melanoma being one of the
00:49most deadly skin cancers.
00:51Can you talk a
00:53little bit about how we have
00:56traditionally treated Melanoma
00:58and where things might be going?
01:01Sure, when we
01:03think about oncologic treatments,
01:05there are three major categories.
01:08You can take a cancer out with surgery,
01:11you can do radiation, or you can
01:14give what we call systemic therapy,
01:17which is therapy that's given by mouth.
01:20But I feel the vast majority of melanomas
01:23are actually discovered really early on
01:26when people see a changing mole
01:28or a dermatologist might find
01:30one on a routine skin exam.
01:32Most of the melanomas are then excised,
01:35in other words, taken out and
01:37nothing further needs to be done,
01:39and patients are simply observed.
01:42Every so often patients come in
01:44without ever knowing that they
01:45had a Melanoma in the skin.
01:47So it's a Melanoma that has
01:49spread beyond the primary site.
01:51Or they might have had a primary
01:53Melanoma that was removed years ago,
01:55but a few cells escaped and are
01:58now developing into tumors in
01:59other locations in the body.
02:01What I do in my clinic is treat with
02:04systemic therapy so things that are
02:06administered by mouth or by IV
02:08so they go all over the body and
02:10that's what we're going to talk about
02:13primarily today.
02:14One of the questions that a lot of
02:17patients have is when they have
02:18that phenomenon of metastatic Melanoma,
02:20so the Melanoma has escaped.
02:22It's gone to other parts of the body
02:25where surgery really can't remove the
02:27Melanoma itself and where
02:29you're treating with systemic therapy
02:31people wonder about the prognosis
02:33and whether in fact they can
02:36never be quote cancer free.
02:37Can you talk a little bit
02:40about that?
02:41When I started treating patients
02:43with metastatic Melanoma in 2001,
02:45if somebody had cancer
02:47that had spread beyond the skin
02:49and into the internal organs,
02:51we would have a frank conversation
02:53with the patient and say we're really sorry,
02:57this is an incurable disease,
02:58and on average people live
03:00between 6 and 12 months.
03:01You should start getting your
03:04affairs in order and we will do
03:06what we can and hope for the best.
03:08At the time we had a chemotherapy called
03:10Dacarbazine and an immunotherapy
03:12called high dose interleukin two which
03:15was very difficult to administer.
03:16The Dacarbazine might have shrunk the
03:18tumors temporarily for a few weeks,
03:20and the high dose interleukin
03:22two would result
03:23in actual cure,
03:24but in a very small percentage of patients,
03:27perhaps 4 or 5%.
03:29Newer therapies were then
03:30developed after that,
03:31and by 2005 or 2006 we were seeing
03:34that the median survival was
03:36actually in the order of one year.
03:39At present we don't actually even
03:41know what the median survival is,
03:43and when a patient comes in
03:45and asks what the prognosis is,
03:47I say at least 50% chance that
03:50we're going to have prolonged
03:52survival and if prolonged,
03:53disease free.
03:55But I can't actually tell people if
03:58the cancer is ever going to come back.
04:02We do believe that we are actually
04:03curing a subset of patients
04:05who have metastatic Melanoma,
04:07including people who've had a lot
04:09of disease and disease
04:11that's gone to vital organs such as the liver,
04:14the lungs,
04:15and the brain.
04:17When you say prolonged disease free survival,
04:19I'm assuming that you mean
04:21more than days or weeks and maybe even
04:24more than a few years. Is that right?
04:27Absolutely. So when we started using
04:28the first of the newer immune therapies,
04:31a drug called ipilimumab
04:37we still have patients who were
04:39treated in those years who have never
04:41required additional treatment and are
04:43disease free and living their lives.
04:45Now I can't say for sure that
04:47it's never going to be a problem,
04:49but the chances are that it's not going
04:52to be a problem over a decade later.
04:54So yes, we're talking about years.
04:57We've talked a little
04:59bit on this show about immune
05:01therapy for a variety of cancers,
05:03but it seems that in metastatic
05:05Melanoma it really seems to
05:07be incredibly effective,
05:08especially when you look
05:10at how far we've come
05:14in 2001 telling people that
05:15they had less than a year,
05:17and to get their affairs in order,
05:20why is it that immunotherapy seems
05:22to work so well in Melanoma but may
05:25not work as well in other cancers?
05:28That's an excellent question.
05:30Melanoma by nature tends to have
05:32more mutations than many other tumors.
05:35It's for the most part a
05:37sun exposed malignancy.
05:39So the sun will cause damage in many,
05:43many genes and because of the multiple
05:46mutations there are a lot of immune
05:49cells that recognize these
05:51cancer cells as foreign or bad and
05:53with time they get exhausted and
05:56these newer drugs will stimulate them.
05:59But we probably have a larger
06:01repertoire of immune cells in
06:03Melanoma than most other cancers,
06:05and that's why they respond better.
06:07And I think another interesting point
06:10to make is that there are
06:13two other types of skin cancers.
06:15There's a fairly rare skin cancer
06:17called Merkel cell carcinoma,
06:19which also has a fair number of
06:21mutations and also some related and
06:23metastatic squamous cell carcinomas and
06:25also will respond very well to immunotherapy,
06:28better than many other tumor types
06:30where we might see response but not for many,
06:34many years as we see in Melanoma.
06:37But we do think it's related to
06:40the tumor mutation burden or the
06:42number of mutations that these cells have.
06:45And so as you think about immunotherapy,
06:48you mentioned that the first
06:51generation of these was actually
06:53brought into practice in 2005, 2006.
06:55Have we developed newer forms
06:58of immunotherapy since then?
06:59And what's the prognosis?
07:01What are some of
07:04the exciting developments that
07:05have happened over the more
07:07recent time?
07:09So there are many exciting developments,
07:11the first drug Ipilimumab
07:13was brought into
07:16clinical trials in those years.
07:18But it actually took many
07:20years to achieve FDA approval.
07:22It was only FDA approved for
07:25metastatic Melanoma in 2011,
07:26so the first Ipilimumab,
07:28results in nice tumor regression,
07:30in maybe 10% of
07:33patient's, but the second generation drug is
07:35a drug that targets a molecule called PD1,
07:38which stands for programmed death one.
07:40There were two that were first
07:42given to patients with Melanoma.
07:45Nivolumab and pembrolizumab,
07:46also known as Opdivo and Keytruda.
07:48Subsequently,
07:49many other companies have developed
07:51drugs that inhibit PD one and
07:53this one seemed to be the better
07:55target for the immunotherapy.
07:57So when we give this to Melanoma patients,
08:00instead of seeing nice responses in maybe 10
08:03percent of patients we will see good
08:05responses in 30 to 40% of patients,
08:08and interestingly,
08:09this is less toxic,
08:10so the second generation was both
08:13more effective and less toxic
08:15than the first generation.
08:17Then the question asked in around 2009,
08:19when we already had a little
08:22bit of experience with these PD one
08:24inhibitors was what would happen
08:26if we give the two drugs together.
08:29So these two classes of drugs
08:32target non redundant pathways
08:33in the immune cell and
08:35its interaction with cancer cells.
08:37So if we inhibited two different
08:39places in theory we will get enhanced
08:41activation of our chief immune cell,
08:44which is called a T cell.
08:45And indeed this was the case, when we
08:48give the two together in Melanoma,
08:50we now see very nice responses
08:52in excess of 55% of patients.
08:55So the two together is better
08:57than either one alone.
08:58Just to clarify,
09:00when you say the two together
09:02you mean Ipilimumab and
09:04pembrolizumab.
09:06The studies have used Ipilimumab
09:08and nivolumab simply because both of
09:10these drugs were developed by the
09:12same company. But yes, it's been
09:14given with pembrolizumab as well,
09:15but not Ipilimumab and
09:17pembrolizumab, which both target
09:18PD 1 correct. There's no point
09:20in giving two drugs that inhibit
09:22the same target concurrently,
09:23so by that point, did we switch all
09:26of our patients to dual therapy?
09:28Actually no, because
09:29remember, some of the patients
09:31do very well with monotherapy.
09:3330-40% will do well with the one drug,
09:36the PD one inhibitor.
09:38So we're trying very hard to select
09:40those patients who are more likely
09:42to respond to one drug and also
09:45patients who might not be able
09:47to tolerate extensive toxicity.
09:49The toxicities are the main problem, it
09:51depends where the patient lives,
09:53how socially and economically
09:54robust they are,
09:55whether they're associated with
09:57a health care system that can
09:59support extensive toxicities,
10:00but when we have patients who've got
10:02aggressive disease and particularly young
10:04patients with no other medical problems,
10:06we do start off with the two drugs up front.
10:10There are other people in the
10:12Melanoma field who might start with
10:15one and then add the second one if
10:18the first one alone does not work.
10:20So a lot of refinement of these
10:22regimens still needs to be done,
10:24and there are many studies looking at how
10:27much to give, when to give, what sequence, etc.
10:30It takes years to sort all of this out.
10:34I also want to add that we now have a third
10:38target that is looking very promising
10:41in Melanoma,
10:42there's a target called LAG-3.
10:44It's an antigen that's expressed
10:47on these same immune cells or T cells,
10:50and when you give inhibitors of LAG-3
10:53together with PD one inhibitors,
10:56it does appear that it's going to be
10:58better than PD one inhibitors alone.
11:01The data are still very new and more
11:03maturity of the data is going to be required.
11:06In other words,
11:07we need to follow patients for much
11:09longer to make sure that it
11:11actually holds up.
11:13Clinical trials for that drug are
11:15currently ongoing.
11:17It's already in a phase three
11:19study which is completed accrual
11:21and the first data do suggest
11:23that the two drugs are better
11:25than the nivolumab alone.
11:27And has anybody thought
11:28about adding Ipilimumab?
11:30Yes, there we again will run into
11:33problems with side effects and we
11:35have to be very careful when we
11:38mix 3 drugs and this takes a
11:41long time to work all of this out.
11:45It sounds like with now the three
11:48kind of tiers of immunotherapy
11:51that you're talking about,
11:53upwards of 55, maybe even
11:55close to 65-75% of patients
11:57might have prolonged
11:59disease free survival.
12:01We don't know yet about the 65-75%.
12:04That's what we're shooting for,
12:05and ultimately,
12:06we're going to shoot for 100%.
12:08I also want to add that this is
12:11just one type of immune therapy.
12:14We call it immune checkpoint inhibitors,
12:17so the checkpoint refers to a negative
12:19regulator of the immune cells,
12:21and that's what these drugs target.
12:24The various other types of cellular
12:27manipulations that we can give to
12:29activate the immune system against cancer,
12:31but the immune checkpoint
12:33inhibitors specifically refers
12:34to molecules on immune cells and
12:37cancer cells that have crosstalk.
12:39They talk to each other and the cancer
12:41cell will suppress an immune cell so
12:43that it remains alive.
12:46And so this is just one approach
12:49to immunotherapy for cancer.
12:51Well, we certainly want to
12:53find out more about the other
12:55approaches to immune therapy.
12:56We talk a lot on this show about
12:59immune checkpoint inhibitors,
13:00but certainly thinking about other ways
13:02that we can use and manipulate the immune
13:05system to fight metastatic Melanoma
13:07will be very exciting to learn about,
13:10but first we're going to take a
13:12short break for a medical minute,
13:14so please stay tuned to learn
13:16more about Melanoma with my
13:18guest Doctor Harriet Kluger.
13:20Funding for Yale Cancer Answers
13:23comes from Smilow Cancer Hospital.
13:2515 care centers offer access to
13:27oncologists committed to providing
13:29patients with cancer and blood diseases
13:31individualized, innovative care.
13:33Find a Smilow Care Center near
13:36you at YaleCancerCenter.org.
13:40The American Cancer Society
13:42estimates that more than 65,000
13:45Americans will be diagnosed with
13:47head and neck cancer this year,
13:49making up about 4% of all cancers.
13:52When detected early,
13:53however, head and neck cancers are
13:56easily treated and highly curable.
13:58Clinical trials are currently
14:00underway at federally designated
14:02Comprehensive cancer centers such
14:04as Yale Cancer Center and at Smilow
14:06Cancer Hospital to test innovative new
14:08treatments for head and neck cancers.
14:11Yale Cancer Center was recently awarded
14:13grants from the National Institutes
14:16of Health to fund the Yale Head
14:18and Neck Cancer Specialized Program
14:21of Research Excellence or SPORE to
14:24address critical barriers to treatment
14:26of head and neck squamous cell
14:28carcinoma due to resistance to immune
14:31DNA damage and targeted therapy.
14:33More information is available at
14:35yalecancercenter.org. You're listening
14:37to Connecticut Public Radio.
14:39Welcome back to Yale Cancer Answers.
14:42This is doctor Anees Chagpar
14:43and I'm joined tonight
14:46by my guest Doctor Harriet Kluger.
14:48We're talking about Melanoma and T cells
14:51and Harriet right before the break we
14:53were talking about these tremendous
14:55advances that have happened in the
14:58treatment of metastatic Melanoma.
15:00For anyone who just joined us,
15:02Harriet was mentioning that when
15:04she started treating metastatic
15:06Melanoma back in 2001,
15:08prognosis wasn't great. Six months.
15:1012 months, but we've now had
15:12a series of immune therapies,
15:14particularly with checkpoint inhibitors
15:16that have really improved the disease
15:19free survival now getting prolonged
15:21survival in over 50% of patients.
15:24But Harriet right before the break
15:26you left us with this little
15:29teaser that there may be other ways
15:32to manipulate the immune system
15:34that are now being investigated.
15:36That might hold promise in metastatic melanoma.
15:39Tell us more.
15:41Thank you and
15:43yes, absolutely.
15:44We have a few teasers and that's
15:46what makes this field so exciting.
15:48So one of the additional classes of
15:51therapies that we give is cellular therapies.
15:53So for Melanoma or solid tumors we
15:56know that we have these immune cells
15:58that live within the tumor but
16:01they keep trying to fight the tumor.
16:04But at some point they get exhausted
16:06and they're no longer capable
16:08of getting rid of tumor cells.
16:11So many years ago at the National
16:13Cancer Institute doctor Rosenberg,
16:14Steve Rosenberg pioneered a treatment
16:16modality whereby he would resect
16:18tumor and then break up all the
16:20different cellular components,
16:22and take the T cells that
16:25originated from within the tumor
16:26and grow them in a Petri dish and
16:29make billions and billions of cells.
16:32Then, in the meanwhile,
16:33he'd bring a patient back and give them
16:36high doses of chemotherapy to make space,
16:38if you will, for these
16:40newest cells that were growing in
16:42the Petri dish and actually are
16:44educated to recognize the tumor.
16:46Then he would infuse those into the
16:48patient after the chemotherapy and
16:49after the space was made and then give
16:52some growth factor called Interleukin
16:53two and then cells within patients
16:55would recover and go home and there
16:57is a subset of patients who were actually
17:00cured from this therapy as well.
17:02It's similar to having a bone
17:04marrow transplant you go in for
17:06a one time shot for a few weeks
17:08and then you go home and live your life.
17:11The initial response rates at the
17:14National Cancer Institute were in
17:15the order of 50%, now with the immune
17:18checkpoint inhibitors we're seeing
17:20lower response rates simply because
17:21many of the patients whose tumors
17:23immune sensitive are actually cured
17:25by the checkpoints that we discussed
17:27in the previous session over here,
17:30but still they work and we have
17:32patients who are cured now from
17:34the cellular therapies.
17:36After they haven't responded to
17:38the immune checkpoint inhibitors,
17:39that gives patients
17:41another option.
17:43This treatment is now being
17:44studied in other cancers as well.
17:46Lung cancer, head neck cancer,
17:48cervical cancer, and so on,
17:50and responses are being seen there too.
17:52In the meanwhile the field
17:54has moved forward and the cellular
17:56therapy is no longer only given
17:58at the National Cancer Institute.
18:00In fact,
18:01at Yale we have a lab that
18:03can manufacture these cells.
18:05There are also companies that are
18:07trying to commercialize this
18:09modality. So you send the tumor
18:11to the company, they grow the cells for you.
18:14They send them back and we give
18:17the treatment in the hospital.
18:19So that is something that likely
18:21will also be on the menu of
18:24options within a year or so
18:26for metastatic Melanoma and in the
18:28future, for other tumor types.
18:30So Harriet just picking up on
18:32that when we think about
18:34things like bone marrow
18:36transplant or other transplants,
18:38anytime we're thinking about putting
18:39cells into somebody, we always
18:41worry about rejection.
18:43So do I have it correct that, what
18:45we're actually doing in this cellular
18:48therapy is taking a patients own tumor?
18:51Taking finding their own T cells
18:53and getting those T cells to grow
18:56and replicate and giving the patient
18:59back their own T cells so that
19:02there's less risk of rejection?
19:04Is that right?
19:05That's right, there's
19:06actually no risk of rejection.
19:08The rejection only happens when
19:10you give somebody another person's
19:12immune cells, but in this case
19:14we're talking about giving a
19:16patient back their own cells,
19:18just amplified to the tune
19:21of billions of cells so that these
19:23are the special cells that recognize
19:26the tumor and can then work against
19:28the tumor.
19:31And one would think that if some
19:35people think that your immune system
19:37is fighting off cancer all the time,
19:41and that people have
19:43quote cancer floating around in them,
19:46and that your immune system kind
19:48of fights all of these little
19:51deformed cells off so that you
19:53don't actually develop a cancer,
19:56if that was true,
19:57then why wouldn't this therapy
19:59work for everybody? Why
20:02do we need the checkpoint inhibitors?
20:06I think the problem is that when
20:09we give the cellular therapy,
20:11sometimes patients have many different
20:13tumors in different locations and we already
20:16know now that melanomas can metastasize.
20:18So it is correct that they all start from
20:21the same clone of cells within the skin,
20:25then they metastasize internally and
20:27you get subclones and daughter clones
20:29and granddaughter clones and so on.
20:31And those next generation
20:33clones might have different mutations.
20:35Now if we remove a tumor to generate the
20:38immune cells from one location,
20:41these cells might not be active against
20:44the tumors in a different location,
20:46so that's one reason that it might not work.
20:50Other reasons for failure are
20:52inability to grow the cells in the
20:55lab so not every cell grows.
20:57The vast majority do,
20:58but there's about 10-15% that do not grow,
21:01and sometimes they just don't
21:03grow enough to substantial quantities
21:05and it's just insufficient to overcome
21:08the tumor cells that are actually there.
21:11And this whole concept of
21:14taking cells, sorting them out,
21:17finding the T cells,
21:19growing them up in a Petri dish,
21:22giving them back to the patient,
21:24it sounds really like a major production,
21:27and so whenever we think about
21:29major productions in medicine,
21:31I always think about how much does that
21:34cost and does insurance cover it?
21:37That's an excellent question.
21:39So at present it's still experimental.
21:42So the company that's making the
21:43cells for us in our current clinical
21:46trial covers the cost of it.
21:48The National Cancer Institute,
21:49when they used to do it,
21:51it was free, but with some it
21:53was covered by the government,
21:55essentially the taxpayer.
21:56But you are right, it is very expensive.
21:58I think we also need to keep in
22:00mind that the immune checkpoint
22:02inhibitors are similarly expensive.
22:04And those can also cost hundreds of
22:06thousands of dollars per patient.
22:08So if you start adding up the
22:10hundreds of thousands of dollars
22:11and you compare it to maybe 200,
22:14$300,000 for a one time
22:15therapy such as cellular therapy,
22:17it's not all that different in terms
22:19of order of magnitude is actually
22:21might be a little bit less expensive,
22:23if anything.
22:25And so getting back to the checkpoint
22:28inhibitors, those are generally
22:29covered by insurance now aren't they?
22:31They are yes, correct.
22:33Other than the experimental
22:35ones, the ones that are
22:37approved are covered.
22:39So it sounds to me like
22:42when you have a patient
22:44with metastatic Melanoma,
22:46your first line of therapy is the
22:48immune checkpoint inhibitors.
22:49If they fail, that cellular
22:51therapy is another option.
22:53What if they fail that?
22:56So if they fail that or sometimes by choice,
22:59we actually have additional
23:00experimental options for patients.
23:02So I had talked about the T
23:05cells that recognize the tumor.
23:07Those are called adaptive immune cells.
23:09In other words,
23:11they've adapted to the cancer.
23:13They have special specific
23:14qualities that recognize that we
23:16also have innate immune cells.
23:18Those are generalized cells that are
23:20floating around in our bodies that have
23:23not developed receptors that recognize
23:25specific abnormalities in cancer cells.
23:27Now those innate immune cells are
23:29another whole army of cells that we can
23:33activate in order to target the cancer,
23:35and sometimes we can co-activate
23:38the innate immune cells
23:39and the adaptive cells,
23:41so we can combine additional drugs to
23:43these immune checkpoint inhibitors.
23:45There are many approaches that are
23:47being taken across the country.
23:49One of the approaches that we're
23:51doing over here is to activate a
23:54group of cells called dendritic cells,
23:57that actually present the
23:59tumor antigen to the T cells
24:02as foreign and then make them
24:05become educated or adapted.
24:07So if we give those two together,
24:09we might have better responses than
24:11using the checkpoint inhibitors alone,
24:13so that's one example of an approach.
24:16There are groups that are targeting a
24:18subset of cells called macrophages,
24:20which are also innate immune cells.
24:23Then we need to think about
24:26what these cells do,
24:28so they secrete substances called cytokines.
24:32Interleukin two, that early drug that I
24:35had mentioned that was approved already
24:37in the 1990s is a type of a cytokine.
24:40Many companies are now developing
24:42novel cytokines,
24:43so either better versions of interleukin
24:45two that bind to the interleukin two
24:48receptors that are more important,
24:50or that bind with a
24:52stronger affinity to the receptors.
24:55And then there are other interleukins,
24:57interleukins that are made by
24:59our cells. So you could have
25:02Interleukin 12, interleukin 18,
25:04interleukin 15,
25:04all of these are being looked
25:07at as drug targets,
25:08and in fact there's a researcher at
25:11Yale who has developed a
25:13drug that is a mimic of interleukin
25:1618 that doesn't get sucked up
25:18by decoy proteins in the body,
25:20so should be more potent and we
25:22will be excited to study that in
25:25the next month or two in the clinic.
25:28There's a trial that's opening
25:30up and we will be administering
25:32that drug to patients who have not
25:34responded to the immune checkpoint
25:36inhibitors both with Melanoma
25:38and other diseases.
25:40So Harriet just to unpack a couple
25:42of the concepts that you mentioned.
25:45It sounds to me like
25:47the activation of both the innate
25:49and the adaptive immune system
25:51just makes intuitive sense.
25:53If you have more
25:55adaptive immune cells and
25:57you pair that with more cells
25:59that are presenting to them the
26:02antigens they need to go after,
26:04it seems like that would
26:06be a better approach.
26:07So is that something that is routinely
26:10being done or is the cellular
26:12therapies that we were talking
26:14about earlier really going after
26:16more of those adaptive cells?
26:18And wouldn't it be better if they
26:20could also grow up in a Petri dish
26:23of patients innate T cells as well?
26:27Well, we can grow it up in a
26:29Petri dish or in the body,
26:31so the whole concept behind
26:33giving cytokines is to grow them
26:34actually in the human.
26:35So we give more of the cytokines
26:37and we grow up both innate
26:39and the adaptive cells.
26:40So these are like growth
26:42factors for these cells.
26:43They should make
26:44them propagate.
26:45So that was going to be my
26:47next question is you talk
26:48about all of these cytokines?
26:50These interleukins with various numbers?
26:52How exactly do they work?
26:55It's sounds now like they just
26:58stimulate the innate immune system.
27:00Is that right?
27:02Both innate and adaptive actually?
27:04So they stimulate both.
27:06So all of those different
27:08numbers reflect molecules that
27:10have different activities.
27:12So some of them will stimulate innate cells
27:15and some stimulate the adaptive cells,
27:17some stimulates suppressor cells.
27:19The biology is getting
27:21more and more complicated.
27:23Well, it's always been complicated.
27:25We're just learning now
27:26how complicated it is,
27:27and every time we look,
27:28we discover that we knew nothing.
27:32And so it sounds like we're
27:34almost coming full circle,
27:36though, because interleukin two
27:37was something that you had talked
27:40about at the very outset, which
27:42really wasn't terribly effective back then.
27:45Why would we think that now
27:47these other interleukins will
27:49be more effective?
27:52Now we have
27:55other bullets to administer with it.
27:58And we understand better how to engineer
28:01them so that they can be more effective.
28:05So the idea is that you would use
28:07these interleukins along with cellular
28:09therapy and or checkpoint inhibitors.
28:11Yes, or if they're so good we might
28:13be able to use them alone.
28:15Time will tell when you have a new
28:17drug you start studying it by itself,
28:20mainly because you want to
28:21look at whether it's toxic,
28:23but you also look a little bit at
28:26the activity so some of them might
28:28end up being active on their own.
28:30We will see.
28:32Doctor Harriet Kluger is a professor
28:34of medicine and medical oncology
28:36at the Yale School of Medicine.
28:38If you have questions the addresses
28:40cancer answers at yale.edu and
28:42past editions of the program are
28:44available in audio and written
28:45form at yalecancercenter.org.
28:47We hope you'll join us next week to
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