Available Technology

Simpler is Better: The Production of Young Cell Cultures from Tumor Infiltrating Lymphocytes (TIL) Yields More Effective Adoptive Cell Transfer (ACT) Immunotherapies

Available for licensing is an improved method of adoptive cell transfer (ACT) immunotherapy that can be utilized to treat a variety of infectious diseases and cancers, most notably melanoma.

At its foundation, ACT involves isolating lymphocytes with high affinity for a particular antigen, expanding those cellsin vitroto produce a greater quantity of reactive cells, and infusing the product cells into patients to attack cells expressing the antigen, such as tumor cells, bacterial cells, or viral particles. Previously utilized ACT procedures have been plagued by technical, regulatory, and logistical problems that have prevented consistently successful clinical outcomes. Through years of research, scientists at the National Institutes of Health (NIH) have made great strides in developing ACT into a viable approach to treat cancer patients. Of note, the ACT protocols developed by NIH scientists have successfully treated patients with refractory metastatic melanoma who started with very few effective treatment options. These NIH scientists have found that isolating cells from the tumor infiltrating lymphocytes (TIL) of a patient tumor sample provides a suitable initial lymphocyte culture for furtherin vitromanipulations. They have also discovered that taking the isolated cells through one cycle of rapid expansion (including exposure to IL-2), rather than multiple cycles, yields lymphocyte cultures with higher affinity and longer persistence in patients. Also, they have found that administering nonmyeloablative lymphodepleting chemotherapy prior to the reinfusion of lymphocytes creates a more favorable environment within patients for the transferred cells to execute target cell killing. These scientists envision that, for an ACT immunotherapy to gain regulatory approval and successfully treat a wide array of patients, it will need to be rapid, reliable, and technically simple. One of the most critical factors to this approach is the generation of effective lymphocyte cultures that will rapidly and repeatedly attack the target cells when infused into patients.

Scientists at the NIH have developed a method of generating CD8+ selected "young" lymphocyte cultures for infusion into cancer patients. Lymphocytes that spend fewer daysin vitrobetween their initial isolation from TIL and their ultimate reinfusion into patients compared to lymphocytes cultured by previous ACT protocols are considered young lymphocyte cultures. Young lymphocytes, typically 19-35 days old when reinfused into patients, exhibit improved proliferation, survival, and enhanced anti-tumor activity within patients to yield greater tumor regression compared to older lymphocytes, typically 44+ days old. Furthermore, the generation of young lymphocyte cultures is more rapid, reliable, and technically easier than previous ACT culturing methods. Young lymphocytes are isolated from TIL, directed against a single isolated tumor cell suspension, enriched for CD8 expression, and rapidly expanded once using autologous feeder cells without testing the culture for antigen specificity.

Technically simpler than previous ACT methods: Decreased number of steps in the procedure and less analysis of the cell cultures prior to reinfusion into patients. -More rapid than previous ACT methods: Adoptively transferred lymphocytes spend fewer days undergoingin vitroculturing, so they are introduced to patients with potentially short life expectancies more quickly. -Reliable, life-saving technology: This technology is anticipated by the inventors to yield greater tumor regression and more objective clinical responses in patients compared to previous ACT protocols and all previously attempted treatments for metastatic melanoma.

Mark Dudley

Lab Representatives
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