Can Cryopreserved Tissue be Used in Clinical Trials?

Yes, absolutely! Cryopreserved tissue is not only used in clinical trials, but it’s becoming increasingly critical and sought-after for many modern clinical trials, especially those in precision oncology and cell/gene therapy. The current standard of FFPE preservation disqualifies you from most of the New Clinical Trials.

Here’s why cryopreserved tissue is valuable for clinical trials:

1. High-Quality Molecular Data from Cryopreserved Tissue:
   • Clinical trials often aim to understand the underlying biology of a disease or the mechanism of action of a new drug. Cryopreserved tissue provides the highest quality DNA, RNA, and proteins, enabling comprehensive genomic, transcriptomic, and proteomic analyses. This is crucial for:
     • Biomarker Discovery and Validation: Identifying specific genetic mutations, gene expressions, or protein profiles that predict a patient’s response to a drug or the likelihood of side effects.
     • Patient Stratification: Grouping patients for trials based on their unique tumor characteristics, ensuring the right drug gets to the right patient.
     • Understanding Drug Resistance: Analyzing tissue from patients who progress on a therapy to understand how the tumor evolved resistance.
2. Viability for Functional Assays:
   • Many cutting-edge clinical trials, particularly in the realm of personalized medicine, require live, viable cells from the tumor. Cryopreserved tissue, when properly thawed, can retain cell viability, allowing for:
     • Ex Vivo Drug Sensitivity Testing: Testing the trial drug directly on patient-derived tumor cells or organoids (mini-tumors grown from your tissue) in the lab to predict individual patient response. This helps tailor treatment and understand why some patients respond while others don’t.
     • Cellular Immunotherapies: For trials involving CAR T-cell therapy, TIL therapy, or personalized cancer vaccines, viable tumor cells may be needed to identify tumor-specific antigens, engineer immune cells, or develop the therapeutic product itself.
     • Patient-Derived Xenografts (PDX models): In some cases, viable tumor tissue can be implanted into immunocompromised mice to create PDX models that mimic the human tumor in a living system, allowing for in vivo testing of trial drugs.
3. Long-Term Resource and Retrospective Analysis:
   • Clinical trials can span many years. Cryopreserved tissue biobanks provide a stable, long-term resource. This allows researchers to:
     • Conduct retrospective analyses: Go back and study samples from patients after a trial has concluded to gain new insights based on emerging technologies or hypotheses.
     • Monitor long-term effects: Assess changes in the tumor’s biology over the course of treatment and follow-up.
4. Flexibility and Logistics:
   • Cryopreservation offers logistical advantages. Instead of needing fresh tissue “just in time” for every test, cryopreserved samples can be banked and then retrieved as needed, providing flexibility for trial scheduling and avoiding delays due to sample availability.

How it works in practice for clinical trials:

• Trial Protocols: Many clinical trial protocols explicitly require or strongly recommend the collection and cryopreservation of tumor tissue (and often blood) at specific time points (e.g., at baseline before treatment, at progression).
• Central Biobanks: Trial sponsors (pharmaceutical companies, academic institutions) often establish central biobanks where samples from all participating sites are sent for standardized processing and storage, ensuring quality and accessibility for research.
• Informed Consent: Patients participating in clinical trials will sign detailed informed consent forms that explain how their biological samples, including cryopreserved tissue, will be used for research purposes within the trial.

In essence, cryopreserved tissue is a cornerstone of modern translational research in clinical trials. It allows for a deeper understanding of disease mechanisms, aids in identifying responsive patient populations, and is often an essential component for developing and testing next-generation therapies.