Tuesday, July 15, 2014

Top Three Biobanking Challenges Today

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.

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 ConferenceDownload the agenda here to see what’s on tap.

SAVE $100. Register here and use code XP1998BLOG.
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