T-cells are a type of white blood cell (lymphocyte), one of the primary components of the immune system. They fight cancer cells and foreign substances, such as viruses and bacteria. They defend the body by identifying the offending agent, binding to it, and alerting the other cells in the immune system to assist in destroying these abnormal invaders.
In some cases, cancer can evade destruction by the immune system either because there are not enough T-cells that have successfully detected cancer or because the tumor lacks antigens that help T-cells recognize them. This leads to cancer progression to a point where it needs to be treated through immunotherapy.
T-cell therapies, also known as adoptive cell therapies or T-cell transfer therapies, are a type of immunotherapy that involve the modification of the patient’s T-cells to make them more effective in fighting cancers.
What Are the Two T-Cell Therapies?
1. TIL Therapy
Tumor-infiltrating lymphocyte (TIL) therapy uses t-lymphocytes found within the tumor as they have already recognized the cancer cells. While these cells have overcome the initial challenge of identifying the abnormal cells, TILs do not naturally generate quickly, and there may not be enough cells to manage the tumor burden.
TILs can be extracted from the patient and expanded in the lab using the protein IL-2. The patient is provided radiation or chemotherapy before re-introducing the TILs cells back into the body.
While TILs modified in the lab can be expanded effectively and retain their anti-tumor functions, clinical trials for melanoma have only shown an average efficacy of 44%, though treatments are still under investigation. Since side effects observed in clinical trials are mild, TIL therapy could offer a safe alternative to traditional chemotherapy.
2. CAR T-Cell Therapy
Similar to TIL therapy, CAR T-cell therapy is a subtype of T-cell transfer therapy. CAR refers to the chimeric antigen receptor engineered in a lab to be expressed within the T-cells extracted from the patient. The chimeric antigen receptor allows the T-cells to recognize and bind to cancer cells without relying on MHC, as some cancers are able to downregulate the MHC molecules, allowing them to avoid detection. CARs also have an antigen-binding domain, which can be modified to attach to specific targets, increasing the possible applications for CAR T-cell therapy in creating tumor-specific treatments.
Currently, the FDA has approved six CAR T-cell therapies for treating hematologic cancers, such as B-Cell cancers and multiple myeloma, as CD19 is the main target of CAR T-cells in these therapies.
CAR T-cell therapy is associated with cytokine release syndrome, a severe adverse effect that may be life-threatening to some patients. It is also associated with the possible development of immune effector cell-associated neurotoxicity syndrome (ICANS), a type of neurotoxicity that mimics strokes. However, management of these side effects is possible by using tocilizumab and steroids.
The Need for More T-Cell Therapies
Melanoma is easily treatable, with a greater than 98% 5-year survival rate if caught early. If diagnosed in late stages, the survival rate decreases to 22%. As TILs are most easily obtained from melanoma, it makes an ideal therapeutic target. With increased research and trials, a safe and more effective TIL therapy for melanoma can provide greater success.
While CAR T-cell therapies have been approved only for hematologic malignancies, there is a need for such a treatment option for solid tumors, such as glioblastoma and pancreatic ductal adenocarcinoma (PDAC). The five-year survival rate for PDAC is less than 6%, and the disease’s incidence is increasing without the availability of an effective and safe treatment. There are currently several ongoing trials investigating possible targets for the treatment of PDAC with CAR T-cell therapy, demonstrating the potential for innovation in the disease space.
Create the Next T-Cell Therapy with Vial
Clinical trials often need CROs’ assistance with various tasks to streamline the process and increase efficiency. Vial Oncology CRO is a tech-enabled, full-service clinical research organization that is re-imagining clinical trials for T-cell therapies.
Powered with technology every step of the way connecting the site startup with an electronic data capture (EDC), eSource, and electronic patient-reported outcomes (ePRO) on one integrated platform, allowing real-time data analysis and decreasing the chances of human error through the elimination of double data entry.
With the help of a ClinOps team specializing in Oncology clinical trials and scientific advisors comprised of industry thought leaders, including immuno-oncology, Vial can help create and run your clinical trial seamlessly.
Vial Oncology CRO also offers fixed-price agreements with zero change orders and site startup in under 30 days for faster, better, and cheaper clinical trials. Contact us to learn how we can help you create the next innovation in T-cell therapy.
