The Memorial Sloan Kettering Center is known
as the premier cancer research
institute in the world. Needless to say,
their research team is well acquainted with some of the challenges the
biobanking industry currently faces today.
Who better to provide the latest on the challenges in the field than Vinagolu
Rajasekhar, a Senior Research
Scientist working on live tissue banking with the Memorial Sloan Kettering
Cancer Center and a speaker at this year’s Biorepositories
and Sample Management Conference. He filled us in on what he sees as the three
biggest hurdles in the industry today as well as a couple of other minor obstacles.
What are some
of the challenges that you’re experiencing in your industry today?
Raj: I am glad that you brought up this
very important point of the present context regarding functional biospecimens
and biorepositories. In fact, this is not only the challenge that we face but
it is also a challenge for all those striving to succeed in clinical
translation studies all over the world. Particularly
as a team member of the Memorial Sloan-Kettering Cancer Center, which you all
know as the world premier cancer research institute and also the cancer clinic,
my perspective to this query is different from what one may normally expect
from industries.
Developing durable and functional therapies against human cancers is the
prime challenge for all of us. This is very difficult task to accomplish unless
we have set up faithful pre-clinical experimental models that closely mimic
that of real time patients’ situations.
Human tumors are generally composed of heterogeneous tissues, I mean multiple cell types within a single tumor mass. So, it becomes important to comprehend well with the science behind the biospecimens we obtain. Present cancer cell line models and also genetically engineered mouse tumor models would never recapitulate the original patient tumor heterogeneity that we all have to deal with during the real time treatment situations. Particularly, as a Working Group Member of Biospecimen Science in the International Society for Biological and Environmental Repositories (ISBER), and also collaborating with Dr. Fay Betsou at the Integrated Biobank of Luxembourg (IBBL), I must also bring to the light that the most cancer therapeutics developed to date all over the world have also relied on the data obtained from conventional bio-repositories of flash frozen bulk tumor specimens, which might not represent the real time clinical situations.
Human tumors are generally composed of heterogeneous tissues, I mean multiple cell types within a single tumor mass. So, it becomes important to comprehend well with the science behind the biospecimens we obtain. Present cancer cell line models and also genetically engineered mouse tumor models would never recapitulate the original patient tumor heterogeneity that we all have to deal with during the real time treatment situations. Particularly, as a Working Group Member of Biospecimen Science in the International Society for Biological and Environmental Repositories (ISBER), and also collaborating with Dr. Fay Betsou at the Integrated Biobank of Luxembourg (IBBL), I must also bring to the light that the most cancer therapeutics developed to date all over the world have also relied on the data obtained from conventional bio-repositories of flash frozen bulk tumor specimens, which might not represent the real time clinical situations.
First, human tumors are also dynamic organs. Thus, they manifest variability in their tissue
heterogeneity during cancer development within an organ. These also add up to
inter- and intra- tumor heterogeneities among different foci of the same cancer
within the same organ and within the same tumor lesion across the radius or
from the center to the margins of the tumor. Therefore, flash frozen tissues
are not harmonized specimens. Studies
based on these biospecimens would not reflect the real time patient situation. We
are increasingly convinced of the significance of patient specific treatments
for cancers from our personal experience with the laboratory bench and at the
patient bedside.
Second, the
conventional biorepositories are exhaustible and cannot be replenished. So now the
prime challenge is to aim at developing live tumor banks that are continuously available,
which is a sort of renewable or replenishable as harmonized biospecimens.
Towards this goal, I and Dr. John
Healey, the Chief of Orthopedic Surgical Oncology are together developing
various live banks of human tumors as viable biorepositories. These live
bio-repositories are nothing but patient derived xenograft (PDX) models of human
cancers. Here upon our internal review board approved consenting of the cancer patients,
we utilize their surgically resected tumor specimens. We transplant the fresh tumor
specimens into immunocompromised rodents (mice for example) and follow the development
of tumor growth.
Essentially, here patient tumor tissues
are transplanted into the mice whose immune system is genetically shut down to
facilitate the tumor take-in, and the growth of PDX as clinically
relevant experimental models. This approach will facilitate us conveniently harvest
sufficient tumor volumes and functionally characterize these tumors at
different developmental stages in vivo and in the laboratories. These PDX
models would, on the other hand, generate the original patient tumor-specific
heterogeneity in real time comparable to that of patient situation. Thus, these
models form clinically relevant experimental models for carrying out functional
pre-clinical studies. For example, any drugs we identify by screening for the
sensitive compounds that affect the growth of the at least early PDX models are
expected to be functional in the real patient tumor microenvironment.
Finally, this live biobanking
approach can be also utilized in co-clinical trials in terminally ill patients
as well as for sharing among different clinical research groups worldwide for facilitating
simultaneous global collaborations with relevant tumor types.
In this process, we also encounter some minor technical challenges as
well.
For example:
1. Isolating cells from human tumors present more complex hurdles than that
of from the so far relied mouse tumors.
2. Each organ human tumor type is different from the other organ tumors
within the same patient. For instance, the tissue of human brain tumor cannot
be the same as another human breast tumor or a liver tumor. So, even to
disassociate and extract these cells in functional from, we need to have sound experimental
skills and intellectual expertise and a few others of minor importance that we
can deal another time.
You can
download the full interview with Vinagolu here.
You can hear more from Vinagolu as well as other leaders in the
biobanking at the Biorepositories and Sample Management Conference. Download the agenda here to see what’s on
tap.
SAVE $100. Register
here and use code XP1998BLOG.
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