Cell Engineering Lab
Principal Investigator: Tim Luetkens M.D.
Cellular immunotherapies have revolutionized the treatment of cancer and changed academic and industry research paradigms. Our goal at the Cell Engineering Lab at the University of Maryland is to solve some of the key problems faced by these new technologies, such as frequent immune escape and the paucity of suitable target antigens.
We are using state-of-the-art protein and cell engineering approaches, such as CRISPR ✂️, label-free kinetics 🧲, antibody phage display 🧬, and CAR/TCR/synNotch T cell engineering 🦠
Working closely with the Fannie Angelos Cellular Therapeutics GMP Lab at the University of Maryland, we are now translating our solutions into clinical products for the treatment of pediatric and adult patients with cancer.
CAR T cell selectivity
Chimeric antigen receptors (CAR) expressed on immune cells are an effective tool to kill cancer cells by binding proteins expressed on the target cells' surface. One of the key challenges of this approach is the relative lack of selectivity of CAR T cells for tumor cells and the resulting targeting of normal tissues also expressing the antigen (on-target off-tumor toxicity). We are developing economical, high-throughput approaches to engineer highly selective antibodies for use as CAR binding domains. In addition, we are developing genetic technologies to restrict CAR T cells from targeting vital healthy tissues.
Targeting immune escape
Cellular immunotherapies often show exceptional initial clinical responses but also frequent relapses as the tumor cells develop strategies to evade the treatment. In addition, some types of cancer generally do not respond to cellular immunotherapies because, at the time of treatment, they have already developed powerful mechanisms to escape the patients' own immune system. Our group is developing new technologies to overcome some of the most common pre-existing and adaptive immune escape mechanisms using non-toxic adoptive cell therapies that render the tumor cells once again vulnerable.
While some cellular immunotherapies have been very successful in a number of hematologic malignancies, for most types of cancer, in particular solid tumors, no effective treatments have been identified to date. Using our rapid antibody/CAR development platform, we are currently exploring several targets in this space and various combinatorial approaches to further shape the selectivity of these cells.
Neelam Bhardwaj Ph.D. (Novartis)
Maria Carter M.D. (Cincinnati Children's Hospital)
Fiorella Iglesias M.D. (Memorial Sloan-Kettering)
Erin Morales M.D. (Texas Children's Hospital/University of Utah)
Michael L. Olson (Dana Farber Cancer Institute)
Sabarinath Venniyil Radhakrishnan M.D. (Medical College of Wisconsin)
Julia Templin Ph.D. (ELIXIR Consultants)
Marcus Stucki B.Sc. (University of Utah)
Christa Shorter B.Sc. (University of Utah)
Erica Vander Mause Ph.D. (Caribou Bio)
Shuping Wang Ph.D.
Siani Weston (University of Utah)
Sara Yousef Ph.D. (Immatics)
Role of immunotherapy in Ewing sarcoma.
J Immunother Cancer. 2020 Dec;8(2):e000653.
Successful transfer of anti-SARS-CoV-2 immunity using convalescent plasma in an MM patient with hypogammaglobulinemia and COVID-19.
Blood Adv. 2020 Oct 13;4(19):4864-4868.
CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide.
Nat Commun. 2020 Feb 7;11(1):798.
In vivo vaccination effect in multiple myeloma patients treated with the monoclonal antibody isatuximab.
Leukemia. 2020 Jan;34(1):317-321.
HIGHLY SELECTIVE CD229 CHIMERIC ANTIGEN RECEPTOR AND USES THEREOF
Publication number: 63285843 (2021)
COMPOSITIONS AND METHODS FOR TREATING WITH CAR T CELLS
Publication number: 63146305 (2021)
UPREGULATING HLA CLASS I ON TUMOR CELLS
Publication number: 62940689 (2020)
CD229 CAR T CELLS AND METHODS OF USE THEREOF
Publication number: 20190330338 (2018)
BINDING MEMBERS WITH ALTERED DIVERSITY SCAFFOLD DOMAINS
Publication number: 20190256840 (2017)