Engineered T-Cell Immunotherapy Approaches in Cancer

A personalized form of immunotherapy called adoptive T-cell transfer is moving beyond a few specialized academic centers to biotechnology and pharmaceutical development. The several types of adoptive T-cell transfer are technically challenging and inherently personalized: a patient’s own T cells are harvested, sometimes modified, and expanded in vitro before being injected back into the patient to better and more specifically attack the cancer. Pharmaceutical companies are now seeing enough clinical evidence to show that this therapy approach can work and are beginning to develop these personalized therapies on a larger scale.

At the 1-day Cancer Immunotherapy: A Long Awaited Reality Conference, held at the New York Academy of Medicine on March 27, immunologists and company scientists discussed the progress and the challenges of developing these personalized immunotherapies.

In 2012, the Switzerland-based Novartis announced a collaboration with the University of Pennsylvania to develop chimeric antigen receptor (CAR) technology, a type of adoptive T-cell transfer therapy, for cancer. On March 31, California-based Kite Pharma, Inc, who focus on developing and commercializing engineered adoptive T-cell therapy, announced that the US Food and Drug Administration (FDA) has granted an orphan drug designation to the company’s autologous engineered T-cell product, which targets CD19-expressing B-cell malignancies, for the treatment of diffuse large B-cell lymphoma.

Cameron Turtle, MD, PhD, an oncologist who focuses on T-cell therapies at Fred Hutchinson Cancer Research Center in Seattle, discussed a CD19-specific CAR-modified T-cell approach. T cells are collected from the patient’s blood, then genetically engineered to express a CAR on their surface. The CARs allow T cells to recognize specific tumor antigens. The CAR-modified T cells are then infused back into the patient, where these T cells are expected to multiply, target, and kill tumor cells. Turtle also works in mouse models to understand how to select patient T cells that have the most potential to proliferate after being infused back into the patient. One of the current limitations of this type of therapy is that not all patients have T cells that can grow in vitro or that will multiply enough to be efficacious once back inside the patient.

MaxCyte, based in Maryland, is developing an instrument platform for ex vivo cellular engineering of autologous or allogeneic cells, allowing engineering without damaging the cell. The company is automating the creation of CAR cells-a limiting step in CAR-based adoptive T-cell therapy.

Another biotechnology company, Adaptimmune, is focused on T-cell therapies to treat cancer, as well as infectious diseases. They focus not on engineering novel receptors on T cells, but on enhancing native T-cell receptors with high affinity to tumor antigens. Current clinical trials in multiple myeloma, melanoma, synovial sarcoma, hepatic cancer, and ovarian cancer are ongoing at select immunotherapy cancer centers, such as the University of Pennsylvania in Philadelphia, Memorial Sloan-Kettering Cancer Center in New York City, and Roswell Park Cancer Institute in Buffalo.

The 4th Annual Cancer Immunotherapy: A Long Awaited Reality Conference at the New York Academy of Medicine in New York City was sponsored by MaidStone Life Sciences LLC.