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Andrea Schmidts - CAR-T Cell Therapies

Research Focus

Chimeric antigen receptor (CAR)-T cells are a promising tool for cancer treatment. CAR-T cells recognize targeted antigens on tumor cell surfaces, kill those cells, and may form memory to enable long-term tumor control. However, like many cancer therapies, disease resistance is a major challenge to CAR-T cell therapy. The focus of my Emmy Noether group is to understand and combat cancer cell resistance to CAR-T cell therapy. We aim to improve this innovative therapeutic approach and extend it to a broader patient population in clinical practice. We have established a high-throughput CRISPR platform that allows for the functional characterization of tumor antigen variants, and we use the newest gene editing technologies to engineer CAR-T cells with improved resilience. Ultimately, we aim to translate resilient CAR-T cell therapies into early-phase clinical trials for cancer patients.

Andrea Schmidts studied medicine in Freiburg (DE) and Aberdeen (UK). In 2013, she started her clinical training in internal medicine with a focus on hematology, oncology, and stem cell transplantation. From 2017-2022, she studied adoptive cell therapies for cancer treatment in Marcela Maus's lab at Massachusetts General Hospital and Harvard Medical School. In 2022, she moved to Munich to start her own Emmy Noether research group at TranslaTUM and the Department of Medicine III.

  • Emmy Noether-Program, German Research Foundation (2022)
  • John Hansen Research Grant, DKMS (2020)
  • Research Fellowship, German Cancer Aid (2018)
  • Scholar, German National Academic Foundation (2008)

Leick, M.B., Silva, H., Scarfò, I., Larson, R., Choi, B.D., Bouffard, A.A., Gallagher, K., Schmidts, A., Bailey, S.R., Kann, M.C., Jan, M., Wehrli, M., Grauwet, K., Horick, N., Frigault, M.J., Maus, M.V. (2022). Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia. Cancer Cell 40(5):494-508.

Larson, R.C., Kann, M.C., Bailey, S.R., Haradhvala, N.J., Llopis, P.M., Bouffard, A.A., Scarfó, I., Leick, M.B., Grauwet, K., Berger, T.R., Stewart, K., Anekal, P.V., Jan, M., Joung, J., Schmidts, A., Ouspenskaia, T., Law, T., Regev, A., Getz, G., Maus, M.V. (2022). CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours. Nature 604(7906):563-570.

Bailey, S.R., Vatsa, S., Larson, R.C., Bouffard, A.A., Scarfo, I., Kann, M.C., Berger, T.R., Leick, M.B., Wehrli, M., Schmidts, A., Silva, H., Lindell, K.A., Demato, A., Gallagher, K., Frigault, M.J., Maus, M.V. (2022). Blockade or deletion of IFNg reduces macrophage activation without compromising CAR-T function in hematologic malignancies. Blood Cancer Discov. 3(2):136-153.

Petri, K.*, Zhang, W.*, Ma, J.*, Schmidts, A.*, Lee, H., Horng, Y.E., Kim, D.Y., Kurt, I.C., Clement, K., Hsu, J.Y., Pinello, L., Maus, M.V., Joung, J.K., Yeh, J.R. (2022). CRISPR prime editing with ribonucleoprotein complexes in zebrafish and primary human cells. Nature Biotechnol. 40(2):189-193. *co-first author

Jan, M., Scarfò, I., Larson, R.C., Walker, A., Schmidts, A., Guirguis, A.A., Gasser, J.A., Słabicki, M., Bouffard, A.A., Castano, A.P., Kann, M.C., Cabral, M.L., Tepper, A., Grinshpun, D.E., Sperling, A.S., Kyung, T., Sievers, Q.L., Birnbaum, M.E., Maus, M.V., Ebert, B.L. (2021). Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide. Sci Transl Med. 13(575):eabb6295.

Schmidts, A., Wehrli, M., Maus, M.V. (2020). Toward Better Understanding and Management of CAR-T Cell-Associated Toxicity. Annu Rev Med 72:365-382.

Schmidts, A., Marsh, L.C., Srivastava, A.A., Bouffard, A.A., Boroughs, A.C., Scarfò, I., Larson, R.C., Bedoya, F., Choi, B.D., Frigault, M.J., Bailey, S.R., Leick, M.B., Vatsa, S., Kann, M.C., Prew, M.S., Kleinstiver, B.P., Joung, J.K., Maus, M.V. (2020). Cell-based artificial APC resistant to lentiviral transduction for efficient generation of CAR-T cells from various cell sources. J Immunother Cancer. 8(2):e000990.

Schmidts, A., Ormhoj, M., Choi, B.D., Taylor, A.O., Bouffard, A.A., Scarfo, I., Larson, R.C., Frigault, M.J., Gallagher, K., Castano, A.P., Riley, L.S., Cabral, M.L., Boroughs, A.C., Velasco Cardenas, R.M., Schamel, W., Zhou, J., Mackay, S., Tai, Y.T., Anderson, K.C., Maus, M.V. (2019). Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma. Blood Adv. 3(21):3248-3260.

Choi, B.D., Yu, X., Castano, A.P., Bouffard, A.A., Schmidts, A., Larson, R.C., Bailey, S.R., Boroughs, A.C., Frigault, M.J., Leick, M.B., Scarfò, I., Cetrulo, C.L., Demehri, S., Nahed, B.V., Cahill, D.P., Wakimoto, H., Curry, W.T., Carter, B.S., Maus, M.V. (2019). CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nature Biotechnol. 37(9):1049-1058.

Schmidts, A., Maus, M.V. (2018) Making CAR T Cells a Solid Option for Solid Tumors. Front Immunol. 9:2593.

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Dr. Andrea Schmidts
Technical University of Munich
School of Medicine
Clinic and Polyclinic for Internal Medicine III
Phone: +49 89 4140 9498