Immune effector cell (IEC) therapies, commonly referred as cell therapies, utilize human cells to cause or enhance an immune response against tumor cells. Following remarkable successes with several patients in the early 2010s – most notably, the case of Emily Whitehead, the first pediatric CAR-T patient, who recently celebrated 10 years of being cancer-free – IECs have become a key focus of investigations to help treat multiple types of cancer, resulting in several approved therapies and hundreds of ongoing trials.
Here, we briefly define the four main groups of IECs currently under research: chimeric antigen receptor T cells (CAR-T), engineered T cell receptor (TCR) T cells, tumor-infiltrating lymphocytes (TILs), and natural killer (NK) cells, with a view towards advantages and disadvantages of each approach.
CAR-Ts: the first and currently only approved IEC therapy, autologous CAR-Ts take advantage of the patient’s own T cells to fight the tumor. Circulating T cells are collected and engineered ex vivo to express a customized receptor, the CAR, which recognizes and binds to a surface protein (antigen) in the tumor cell, inducing cell death.
CAR-Ts can also be generated from allogeneic sources (i.e., T cells collected from healthy donors rather than the patient’s own T cells), reducing costs and shortening time to treatment; however, allogeneic cells require additional precautions to prevent graft vs. host disease. Data for allogeneic CAR-Ts remains in the early stages, and no allogeneic CAR-Ts have been approved so far.
TCR Ts: as in autologous CAR-Ts, T cells are collected and engineered ex vivo, in this case, to express engineered TCRs. The chosen receptor usually derives from a library of endogenous TCRs that are known to target tumor-associated antigens.
TILs: unlike CAR- and TCR-Ts, TIL therapies are not engineered to target a specific antigen; instead, they are naturally occurring T cells with antitumor activity. TILs are collected from a solid tumor sample, separated from the tumor cells, expanded ex vivo, and tested for tumor recognition. The lymphocytes (T cells) that successfully target and kill tumor cells are delivered back to the patient.
NK cells: a rapidly emerging field in IEC, NK cells play a role in immunosurveillance and are guided to tumor sites by chemokines and their associated receptors. NK cells do not naturally express TCRs but could be engineered to express TCRs or CARs.
There are now six autologous CAR-T therapies approved by the FDA, all of which target either CD19 (for ALL and non-Hodgkin’s lymphoma) or BCMA (for multiple myeloma). These therapies have demonstrated high and durable response rates in late-stage diseases, which are likely to be cures in some cases.
All these successes have come in hematologic malignancies, but even in those indications, less than 50% of patients achieve long-term remissions. Therefore, there is substantial room for improvement, and many next-generation approaches are under investigation, including multi-antigen targeting, resistance to immunosuppression, and checkpoint inhibition.
New approaches aim to both improve outcomes in hematologic malignancies and drive meaningful efficacy in solid tumors, which are more complex and difficult to treat. Furthermore, cost and time requirements will drive advances in allogeneic, off-the-shelf products and point-of-care manufacturing with the goal of expanding accessibility of these life-saving therapies.
To facilitate understanding and tracking of the complex and rapidly growing field of IEC therapies, SAI’s team of experts has developed CellTraQ, a comprehensive database of cell therapy assets and clinical trials. Whether you want to discuss our strategic consulting capabilities in Oncology or discover the power of CellTraQ, please contact us today.
CellTraQ data search of oncology studies involving T and NK cells divided by tumor type.